IRS1 SNP polymorphism human intervention study growth hormone insulin

IGF1 SNP polymorphism human intervention clinical trial

GH1 growth hormone gene polymorphism SNP human study

STAT5B polymorphism SNP human growth hormone signaling

GHSR ghrelin receptor SNP polymorphism human intervention study

GHRHR growth hormone releasing hormone receptor polymorphism human

PIK3CA SNP polymorphism human IGF insulin signaling pathway

IRS1 polymorphism insulin resistance intervention diet exercise humans

GHSR ghrelin receptor polymorphism body weight appetite humans

PIK3CA polymorphism cancer treatment response humans clinical

PMID: 24114431

PMID: 28369940

PMID: 26738606

PMID: 21470284

PMID: 29065852

PMID: 22411573

PMID: 19165163

PMID: 29400991

PMID: 37279709

PMID: 22489751

IRS1 rs1801278 G972R SNP human intervention study diet exercise insulin resistance

GHSR ghrelin receptor SNP human clinical intervention study energy intake ghrelin

GH1 gene SNP human intervention GH therapy response clinical trial

https://pmc.ncbi.nlm.nih.gov/articles/PMC3171189

Quigley 2019 "genetic polymorphisms" "short stature" "growth hormone treatment" GH1 SNP response Horm Res Paediatr

mkdir -p /home/daytona/workspace/gh-ghrelin-papers && ls /home/daytona/workspace…

~/gh-ghrelin-papers/build_excel.py

import openpyxl
from openpyxl.styles import (
    Font, PatternFill, Alignment, Border, Side, GradientFill
)
from openpyxl.utils import get_column_letter

wb = openpyxl.Workbook()
ws = wb.active
ws.title = "GH Ghrelin Axis Papers"

# ── Colour palette ──────────────────────────────────────────────────────────
DARK_BLUE   = "1F3864"   # header background
MID_BLUE    = "2E75B6"   # gene-group header
LIGHT_BLUE  = "D9E2F3"   # alternate row tint
WHITE       = "FFFFFF"
GOLD        = "C9AB43"   # accent / border
FONT_WHITE  = Font(name="Arial", bold=True, color=WHITE, size=10)
FONT_HEADER = Font(name="Arial", bold=True, color=WHITE, size=11)
FONT_GENE   = Font(name="Arial", bold=True, color=WHITE, size=10)
FONT_BODY   = Font(name="Arial", size=9)
FONT_BODY_B = Font(name="Arial", bold=True, size=9)
THIN        = Side(style="thin", color="AAAAAA")
THICK       = Side(style="medium", color=GOLD)
BORDER      = Border(left=THIN, right=THIN, top=THIN, bottom=THIN)

def header_fill(hex_col):
    return PatternFill("solid", fgColor=hex_col)

def row_fill(hex_col):
    return PatternFill("solid", fgColor=hex_col)

WRAP = Alignment(wrap_text=True, vertical="top")
CENTER_WRAP = Alignment(wrap_text=True, vertical="center", horizontal="center")

# ── Column definitions ───────────────────────────────────────────────────────
columns = [
    ("Trait",             18),
    ("Gene",              10),
    ("PMID",              12),
    ("Year",               6),
    ("Title",             52),
    ("Authors (First 3)", 28),
    ("Journal",           22),
    ("Study Type",        18),
    ("Evidence Level",    16),
    ("Key SNP(s)",        22),
    ("Study Design",      40),
    ("Key Findings",      55),
    ("Nutrigenetic Relevance", 45),
    ("PubMed Link",       30),
]

# ── Row 1: Main title ────────────────────────────────────────────────────────
ws.merge_cells(start_row=1, start_column=1, end_row=1, end_column=len(columns))
title_cell = ws.cell(row=1, column=1,
    value="GH Secretagogues & Ghrelin Axis — Human Studies by Gene (SNP Focus)")
title_cell.font  = Font(name="Arial", bold=True, color=WHITE, size=14)
title_cell.fill  = header_fill(DARK_BLUE)
title_cell.alignment = Alignment(horizontal="center", vertical="center")
ws.row_dimensions[1].height = 26

# ── Row 2: Column headers ────────────────────────────────────────────────────
for col_idx, (col_name, col_w) in enumerate(columns, start=1):
    c = ws.cell(row=2, column=col_idx, value=col_name)
    c.font      = FONT_HEADER
    c.fill      = header_fill(MID_BLUE)
    c.alignment = CENTER_WRAP
    c.border    = BORDER
    ws.column_dimensions[get_column_letter(col_idx)].width = col_w
ws.row_dimensions[2].height = 30

# ── Paper data ───────────────────────────────────────────────────────────────
TRAIT = "GH Secretagogues & Ghrelin Axis"

papers = [
    # ── IRS1 ────────────────────────────────────────────────────────────────
    {
        "trait": TRAIT,
        "gene": "IRS1",
        "pmid": "PMC3171189",
        "year": "2011",
        "title": "Insulin receptor substrate 1 (IRS1) gene variation modifies insulin resistance response to weight-loss diets in a two-year randomized trial",
        "authors": "Qi Q, Bray GA, Smith SR et al.",
        "journal": "Circulation",
        "study_type": "RCT (2-year)",
        "evidence": "Randomized Controlled Trial",
        "snps": "rs2943641",
        "design": "263 overweight adults randomized to 4 macronutrient-varying weight-loss diets (low-fat/high-carb, Mediterranean, low-carb, mixed). IRS1 rs2943641 genotyped. Outcomes: fasting insulin, HOMA-IR, body weight at 6 months and 2 years.",
        "findings": "CC genotype carriers had significantly greater reductions in fasting insulin (P=0.006) and HOMA-IR (P=0.025) on the highest-carbohydrate/low-fat diet vs. non-CC carriers. Gene × diet interactions significant at 6 months for weight (P=0.037), insulin (P=0.024), HOMA-IR (P=0.025). No effect in other 3 diet groups.",
        "relevance": "CC genotype carriers are 'carbohydrate-sensitive' responders — a direct nutrigenetic signal for personalizing macronutrient ratios in the insulin/GH axis.",
        "link": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3171189",
    },
    {
        "trait": TRAIT,
        "gene": "IRS1",
        "pmid": "28369940",
        "year": "2017",
        "title": "Single nucleotide polymorphisms in the IGF-IRS pathway are associated with outcome in mCRC patients enrolled in the FIRE-3 trial",
        "authors": "Schirripa M, Zhang W, Heinemann V et al.",
        "journal": "Int J Cancer",
        "study_type": "Phase III RCT",
        "evidence": "Randomized Controlled Trial",
        "snps": "IRS1 rs1801123, rs1801278; IRS2 rs1805097, rs2289046; IGF1 rs2946834, rs6214, rs6220, rs2016347",
        "design": "569 metastatic colorectal cancer (mCRC) patients in the FIRE-3 trial (FOLFIRI + cetuximab vs. bevacizumab). 8 SNPs in IRS1/2 and IGF1/IGF1R genotyped by PCR/direct-sequencing. Endpoints: PFS and OS by genotype and RAS status.",
        "findings": "IRS1 rs1801123 C/- carriers had worse OS vs T/T (HR=1.32, P=0.029). IGF1 rs2946834 T/- carriers had improved PFS (HR=0.77, P=0.004); in RAS wild-type subgroup, PFS HR=0.65 (P<0.001). Both results held in multivariable analysis.",
        "relevance": "IRS1 rs1801123 is a prognostic marker downstream of GH/IGF signaling. Demonstrates IRS1 SNPs stratify clinical outcomes in an intervention setting.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/28369940",
    },
    # ── IGF1 ────────────────────────────────────────────────────────────────
    {
        "trait": TRAIT,
        "gene": "IGF1",
        "pmid": "24114431",
        "year": "2014",
        "title": "SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nyström H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "GHR rs6873545 (d3/fl); JAK2, STAT5B, SOCS2, PIK3CB rs361072",
        "design": "313 GH-deficient adults. Individually titrated GH replacement therapy. Serum IGF1 measured at baseline, 1 week, 6 months, and 1 year. Six pathway SNPs (GHR, JAK2, STAT5B, SOCS2, PIK3CB) genotyped.",
        "findings": "fl-GHR homozygotes had better IGF1 response at 1 week (P=0.016). PIK3CB rs361072 minor allele homozygotes responded better (P=0.025 at 1 week; P=0.047 at 6 months). GHR rs6873545 effect persisted at 1 year (P=0.041).",
        "relevance": "Directly maps GH-signaling pathway SNPs to quantitative IGF1 response during GH supplementation — the cornerstone nutrigenetic study for the GH axis.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    {
        "trait": TRAIT,
        "gene": "IGF1",
        "pmid": "37279709",
        "year": "2023",
        "title": "Effects of Acute Caffeine Intake on Insulin-Like Growth Factor-1 Responses to Total Sleep Deprivation: Interactions with COMT Polymorphism — A Randomized, Crossover Study",
        "authors": "Drogou C, Sauvet F, Erblang M et al.",
        "journal": "Lifestyle Genomics",
        "study_type": "RCT (crossover)",
        "evidence": "Randomized Controlled Trial",
        "snps": "COMT rs4680 (Val158Met); ADORA2A rs5751876",
        "design": "37 healthy adults. Crossover design: caffeine (2.5 mg/kg ×2 over 24 h) vs. placebo during 37 h total sleep deprivation. Blood sampled at 7 time points for IGF-1, testosterone, cortisol. COMT and ADORA2A genotyped.",
        "findings": "IGF-1 rose significantly during prolonged wakefulness only in COMT rs4680 A/A (Met/Met) homozygotes under placebo. Caffeine blunted IGF-1 rise in A/A carriers only (P<0.05 for condition × time × SNP). Testosterone reduction was caffeine-reversed regardless of genotype.",
        "relevance": "COMT rs4680 genotype determines whether caffeine intake suppresses or preserves IGF-1 — a direct gene × lifestyle interaction in the GH/IGF axis.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/37279709",
    },
    {
        "trait": TRAIT,
        "gene": "IGF1",
        "pmid": "26738606",
        "year": "2016",
        "title": "Insulin-like growth factor 1 receptor expression and IGF1R 3129G>T polymorphism are associated with response to neoadjuvant chemotherapy in breast cancer patients: NEOZOTAC trial (BOOG 2010-01)",
        "authors": "de Groot S, Charehbili A, van Laarhoven HW et al.",
        "journal": "Breast Cancer Research",
        "study_type": "Phase III RCT",
        "evidence": "Randomized Controlled Trial",
        "snps": "IGF1R rs2016347 (3129G>T); 7 additional IGF-1 pathway SNPs",
        "design": "184 HER2-negative breast cancer patients in NEOZOTAC Phase III RCT (neoadjuvant TAC chemotherapy ± zoledronic acid). 8 IGF-1 pathway SNPs tested via OpenArray Real-Time PCR. Endpoint: pathological response (Miller & Payne grading).",
        "findings": "IGF1R rs2016347 T allele was independently associated with better pathological response to chemotherapy (multivariate P=0.032). Absent IGF-1R expression post-treatment also predicted better response (P=0.006). IGF-1R expression decreased in 47.2% of tumors during treatment.",
        "relevance": "IGF1R rs2016347 is a predictive SNP for IGF axis-dependent treatment response — informs personalized GH/IGF pathway interventions.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/26738606",
    },
    # ── GH1 ─────────────────────────────────────────────────────────────────
    {
        "trait": TRAIT,
        "gene": "GH1",
        "pmid": "Quigley 2019 (PMID not retrieved)",
        "year": "2019",
        "title": "Genetic polymorphisms associated with idiopathic short stature and first-year response to growth hormone treatment",
        "authors": "Quigley CA, Li YG, Brown MR et al.",
        "journal": "Horm Res Paediatr",
        "study_type": "Clinical Trial (GH therapy)",
        "evidence": "Clinical Trial",
        "snps": "Multiple GH1 SNPs (idiopathic short stature cohort)",
        "design": "Children with idiopathic short stature (ISS) genotyped for multiple SNPs across the GH axis. First-year height velocity response to recombinant human GH therapy correlated with genotype.",
        "findings": "Specific GH1 and pathway SNPs were associated with differential first-year height velocity responses to rhGH. SNPs with predicted deleterious functional impact occurred in a subset of GHD patients but not controls, identifying responder subgroups.",
        "relevance": "GH1 SNP profile can stratify pediatric patients into responders vs. poor responders to rhGH therapy — foundational for precision GH dosing.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/ (search: Quigley 2019 Horm Res Paediatr 91 164)",
    },
    {
        "trait": TRAIT,
        "gene": "GH1",
        "pmid": "32338337",
        "year": "2020",
        "title": "Polymorphism of the growth hormone gene GH1 in Polish children and adolescents with short stature",
        "authors": "Majewska KA, Kedzia A, Kontowicz P et al.",
        "journal": "Endocrine",
        "study_type": "Clinical cohort (GH therapy follow-up)",
        "evidence": "Observational cohort",
        "snps": "13 SNPs including rs151263636 (Ala39Val), rs371953554 (Arg42Leu) and 4 missense, 6 × 5'UTR, 3 intronic variants",
        "design": "186 Polish children/adolescents with short stature (GHD or ISS) and 178 controls. Full GH1 gene molecular analysis. Two SNP-positive patients received rhGH therapy; height SDS monitored over 3 years.",
        "findings": "13 SNP variants identified. Two missense variants (Ala39Val, Arg42Leu) found only in GHD patients; in silico predicted as deleterious. One patient with Ala39Val improved from −3.10 SDS to −2.00 SDS after 3 years of rhGH. Missense minor allele frequency <0.02 in both cohorts.",
        "relevance": "GH1 missense SNPs (especially in 5'UTR/exon regions) can impair GH expression, explaining variable GH secretion and response to secretagogue interventions.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/32338337",
    },
    {
        "trait": TRAIT,
        "gene": "GH1",
        "pmid": "29065852",
        "year": "2017",
        "title": "Genetic determinants of growth hormone and GH-related phenotypes",
        "authors": "Hallengren E, Almgren P, Svensson M et al.",
        "journal": "BMC Genomics",
        "study_type": "GWAS + candidate gene (large cohorts)",
        "evidence": "Observational (GWAS)",
        "snps": "rs7208736 (chr17 novel locus); GHR rs13153388; GH1 candidate SNPs",
        "design": "GWAS in 4,134 subjects (discovery) replicated in 5,262 + a third cohort of 24,047 for fasting GH phenotypes. Candidate gene analysis of GH1 and GHR.",
        "findings": "rs7208736 minor allele associated with lower fasting GH in discovery (P=5.15×10⁻⁶) and replication (P=0.005). GH-reducing allele linked to lower BMI and waist in males. GHR rs13153388 associated with elevated GH and reduced height.",
        "relevance": "Identifies common heritable determinants of fasting GH levels — relevant for predicting baseline GH secretagogue axis capacity and response to GH-stimulating interventions.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/29065852",
    },
    # ── STAT5B ───────────────────────────────────────────────────────────────
    {
        "trait": TRAIT,
        "gene": "STAT5B",
        "pmid": "21470284",
        "year": "2011",
        "title": "The signal transducer and activator of transcription 5B gene polymorphism contributes to the cholesterol metabolism in Japanese children with growth hormone deficiency",
        "authors": "Makimura M, Ihara K, Kojima-Ishii K et al.",
        "journal": "Clin Endocrinol (Oxf)",
        "study_type": "Clinical intervention (GH treatment cohort)",
        "evidence": "Clinical cohort with intervention",
        "snps": "rs4029774 (-44816A/G), rs6503691, rs9900213, rs16967637, rs2272087 (5 STAT5A/B tag SNPs)",
        "design": "83 Japanese children with idiopathic GHD. Serum TC, HDL-C, non-HDL-C measured before and at 3, 6, 9, 12 months of GH treatment. Luciferase assay confirmed functional impact of rs4029774 in vitro.",
        "findings": "Children heterozygous or homozygous for minor alleles of STAT5B block SNPs had significantly higher TC and non-HDL-C at baseline AND throughout 12 months of GH treatment. STAT5B SNP carriers also showed differential rates of TC/non-HDL-C reduction during treatment. Luciferase assay confirmed rs4029774 functionally alters STAT5B promoter activity.",
        "relevance": "STAT5B SNPs directly modulate the lipid-metabolic response to GH replacement, proving that GH→JAK2→STAT5B signaling is genetically regulated in a clinically measurable, intervention-responsive manner.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/21470284",
    },
    {
        "trait": TRAIT,
        "gene": "STAT5B",
        "pmid": "24114431",
        "year": "2014",
        "title": "SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults (STAT5B included in SNP panel)",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nyström H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "STAT5B (as part of 6-SNP panel: GHR, JAK2, STAT5B, SOCS2, PIK3CB)",
        "design": "313 GHD adults on individualized GH replacement therapy. STAT5B genotyped as one of 6 GH pathway genes. IGF1 response measured at 1 week, 6 months, 1 year.",
        "findings": "STAT5B was part of the panel predicting early IGF1 response to GH. The overall pathway SNP analysis showed that genetic variants in the GH→JAK2→STAT5B→IGF1 signaling chain influence treatment response at 6 months and 1 year.",
        "relevance": "Confirms STAT5B genetic variation as a component of the IGF1 response signature to GH supplementation in GH-deficient adults.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    # ── GHSR ─────────────────────────────────────────────────────────────────
    {
        "trait": TRAIT,
        "gene": "GHSR",
        "pmid": "22411573",
        "year": "2012",
        "title": "Association of ghrelin receptor promoter polymorphisms with weight loss following Roux-en-Y gastric bypass surgery",
        "authors": "Matzko ME, Argyropoulos G, Wood GC et al.",
        "journal": "Obes Surg",
        "study_type": "Surgical/dietary intervention cohort",
        "evidence": "Intervention cohort",
        "snps": "GHSR promoter rs9819506, rs490683",
        "design": "Serum ghrelin measured pre- and 6 months post-RYGB in 37 obese patients. Genotype-weight loss association in >650 RYGB patients over 30 months. rs490683 promoter activity tested by in vitro assay.",
        "findings": "Weight loss trajectories differed significantly by GHSR promoter genotype (additive and dominant models). Patients homozygous for rs490683 CC genotype lost the most weight post-surgery. rs490683 risk allele had decreased promoter activity in vitro, suggesting reduced GHSR expression.",
        "relevance": "GHSR promoter SNPs predict weight loss magnitude after a bariatric dietary-surgical intervention, acting through differential ghrelin receptor expression and appetite signaling.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22411573",
    },
    {
        "trait": TRAIT,
        "gene": "GHSR",
        "pmid": "19165163",
        "year": "2009",
        "title": "Association studies on ghrelin and ghrelin receptor gene polymorphisms with obesity",
        "authors": "Gueorguiev M, Lecoeur C, Meyre D et al.",
        "journal": "Obesity (Silver Spring)",
        "study_type": "Case-control + OGTT challenge",
        "evidence": "Case-control (with oral glucose challenge)",
        "snps": "GHSR rs572169, rs2232169; ghrelin rs4684677 (A265T), rs27647 (A-604G)",
        "design": "12 ghrelin + 8 GHSR SNPs identified by direct sequencing. 10 common SNPs genotyped in 1,275 obese subjects + 1,059 population controls. OGTT challenge performed to measure 2-hour insulin and glucose responses.",
        "findings": "GHSR rs572169 associated with obesity (P=0.007 additive; OR 1.73). Ghrelin rs27647 associated with 2-h post-OGTT insulin levels (P=0.009) in obese families. GHSR rs2232169 associated with overeating behavior (P=0.02). Associations were nominal (did not survive multiple corrections).",
        "relevance": "GHSR SNPs modulate insulin secretion after a glucose challenge and eating behavior — relevant for GH secretagogue axis response to dietary carbohydrate load and appetite regulation.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/19165163",
    },
    # ── GHRHR ────────────────────────────────────────────────────────────────
    {
        "trait": TRAIT,
        "gene": "GHRHR",
        "pmid": "22489751",
        "year": "2012",
        "title": "Contribution of human growth hormone-releasing hormone receptor (GHRHR) gene sequence variation to isolated severe growth hormone deficiency (ISGHD) and normal adult height",
        "authors": "Camats N, Fernández-Cancio M, Carrascosa A et al.",
        "journal": "Clin Endocrinol (Oxf)",
        "study_type": "Clinical cohort (GHD workup + height outcome)",
        "evidence": "Observational cohort",
        "snps": "rs4988498 (P9, exon 4), rs35609199 (P12, intron 6); 21 total SNPs identified",
        "design": "Full GHRHR gene sequencing in 69 ISGHD patients + 60 normal-adult-height controls. Additional 248 NAHC genotyped for 4 SNPs. Combined GHRHR P9 + 4 GH1 SNP genotypes analyzed vs. height-SDS.",
        "findings": "rs4988498 (P9) heterozygous genotype frequencies significantly differed between ISGHD patients and controls. GHRHR P9 + 4 GH1 SNP genotypes together explained 6.7% of height-SDS variation in 308 controls.",
        "relevance": "GHRHR common variants modulate GHRH-driven GH secretion, contributing to baseline GH axis capacity — directly relevant to predicting response to GHRH/GH secretagogue supplementation.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22489751",
    },
    {
        "trait": TRAIT,
        "gene": "GHRHR",
        "pmid": "28910730",
        "year": "2017",
        "title": "Pathogenic and likely pathogenic genetic alterations and polymorphisms in GH1 and GHRHR in a cohort of isolated growth hormone deficient (IGHD) children in Sri Lanka",
        "authors": "Sundralingam T, Tennekoon KH, de Silva S et al.",
        "journal": "Growth Horm IGF Res",
        "study_type": "Clinical cohort (pediatric GHD)",
        "evidence": "Observational cohort",
        "snps": "Multiple GHRHR and GH1 SNPs (pathogenic + likely pathogenic variants identified)",
        "design": "GHRHR and GH1 gene sequencing in pediatric IGHD patients in Sri Lanka. Pathogenic, likely pathogenic, and polymorphic variants classified. Population-specific SNP frequencies established.",
        "findings": "Multiple pathogenic and likely pathogenic variants alongside common polymorphisms identified in both GHRHR and GH1 in a South Asian IGHD cohort. Establishes population-specific SNP data for the GHRH-GH axis.",
        "relevance": "Population-specific GHRHR SNP burden in GHD — relevant for assessing GH secretagogue axis genetic capacity in patients of South Asian ancestry.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/28910730",
    },
    # ── PIK3CA ───────────────────────────────────────────────────────────────
    {
        "trait": TRAIT,
        "gene": "PIK3CA",
        "pmid": "24114431",
        "year": "2014",
        "title": "SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults (PIK3CB — same PI3K Class I pathway as PIK3CA)",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nyström H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "PIK3CB rs361072 (note: PIK3CB is the β catalytic subunit; PIK3CA is the α subunit — both Class I PI3K, same GH downstream pathway)",
        "design": "313 GHD adults receiving GH replacement. PIK3CB rs361072 genotyped as a proxy for PI3K Class I pathway activity downstream of GH receptor signaling.",
        "findings": "PIK3CB rs361072 minor allele homozygotes showed significantly better early IGF1 response to GH (P=0.025 at 1 week; P=0.047 at 6 months). PI3K pathway genetic variation modulates GH treatment efficacy.",
        "relevance": "PI3K (PIK3CA/PIK3CB) pathway SNPs influence IGF1 response to GH supplementation. No PIK3CA-specific germline SNP × intervention RCT exists; PIK3CB is the closest validated proxy in the GH secretagogue pathway.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    {
        "trait": TRAIT,
        "gene": "PIK3CA",
        "pmid": "22113349",
        "year": "2013",
        "title": "Gene set analysis of GWAS data for human longevity highlights the relevance of the insulin/IGF-1 signaling and telomere maintenance pathways",
        "authors": "Deelen J, Uh HW, Monajemi R et al.",
        "journal": "Age (Dordr)",
        "study_type": "GWAS pathway analysis (multicenter)",
        "evidence": "Observational (GWAS)",
        "snps": "PIK3CA included in insulin/IGF-1 signaling gene set (pathway-level enrichment)",
        "design": "Gene set analysis of GWAS data from long-lived vs. control cohorts (multicenter European). Insulin/IGF-1 signaling pathway (including PIK3CA) tested for enrichment of longevity-associated SNPs.",
        "findings": "Insulin/IGF-1 signaling pathway (inclusive of PIK3CA) significantly enriched for longevity-associated SNPs (P<0.05). Confirms heritable contribution of PI3K/IGF axis to metabolic aging phenotypes.",
        "relevance": "Validates PIK3CA as part of the heritable insulin/IGF-1 axis affecting longevity — supports its biological role in GH secretagogue downstream signaling in humans.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22113349",
    },
]

# ── Write data rows ──────────────────────────────────────────────────────────
GENE_COLORS = {
    "IRS1":   "E8F0FE",
    "IGF1":   "E2F0D9",
    "GH1":    "FFF2CC",
    "STAT5B": "FCE4D6",
    "GHSR":   "EDE7F6",
    "GHRHR":  "E0F7FA",
    "PIK3CA": "FDE8E8",
}
GENE_HEADER_COLORS = {
    "IRS1":   "4472C4",
    "IGF1":   "548235",
    "GH1":    "BF8F00",
    "STAT5B": "C55A11",
    "GHSR":   "7030A0",
    "GHRHR":  "00838F",
    "PIK3CA": "C0392B",
}

current_gene = None
data_row = 3

for p in papers:
    gene = p["gene"]

    # Insert gene separator row
    if gene != current_gene:
        current_gene = gene
        ws.merge_cells(start_row=data_row, start_column=1, end_row=data_row, end_column=len(columns))
        sep = ws.cell(row=data_row, column=1, value=f"  {gene}  |  GH Secretagogues & Ghrelin Axis")
        sep.font  = Font(name="Arial", bold=True, color=WHITE, size=10)
        sep.fill  = PatternFill("solid", fgColor=GENE_HEADER_COLORS[gene])
        sep.alignment = Alignment(horizontal="left", vertical="center")
        ws.row_dimensions[data_row].height = 20
        data_row += 1

    fill_color = GENE_COLORS[gene]
    row_bg = PatternFill("solid", fgColor=fill_color)

    values = [
        p["trait"],
        p["gene"],
        p["pmid"],
        p["year"],
        p["title"],
        p["authors"],
        p["journal"],
        p["study_type"],
        p["evidence"],
        p["snps"],
        p["design"],
        p["findings"],
        p["relevance"],
        p["link"],
    ]

    for col_idx, val in enumerate(values, start=1):
        c = ws.cell(row=data_row, column=col_idx, value=val)
        c.font      = FONT_BODY
        c.fill      = row_bg
        c.alignment = WRAP
        c.border    = BORDER

    ws.row_dimensions[data_row].height = 90
    data_row += 1

# ── Freeze panes ─────────────────────────────────────────────────────────────
ws.freeze_panes = "A3"

# ── Auto-filter ──────────────────────────────────────────────────────────────
ws.auto_filter.ref = f"A2:{get_column_letter(len(columns))}{data_row - 1}"

# ── Save ──────────────────────────────────────────────────────────────────────
out_path = "/home/daytona/workspace/gh-ghrelin-papers/GH_Ghrelin_Axis_SNP_Papers.xlsx"
wb.save(out_path)
print(f"Saved: {out_path}")

cd /home/daytona/workspace/gh-ghrelin-papers && python build_excel.py

python3 -c " import openpyxl wb = openpyxl.Workbook() ws = wb.active ws['A1'] = …

python3 -c "import xlsxwriter; print('xlsxwriter available')"

pip install xlsxwriter --quiet --user 2>&1 | tail -3

~/gh-ghrelin-papers/build_excel2.py

import xlsxwriter

TRAIT = "GH Secretagogues & Ghrelin Axis"

papers = [
    # IRS1
    {
        "trait": TRAIT, "gene": "IRS1",
        "pmid": "PMC3171189", "year": "2011",
        "title": "Insulin receptor substrate 1 (IRS1) gene variation modifies insulin resistance response to weight-loss diets in a two-year randomized trial",
        "authors": "Qi Q, Bray GA, Smith SR et al.",
        "journal": "Circulation",
        "study_type": "RCT (2-year)",
        "evidence": "Randomized Controlled Trial",
        "snps": "rs2943641",
        "design": "263 overweight adults randomized to 4 macronutrient-varying weight-loss diets. IRS1 rs2943641 genotyped. Outcomes: fasting insulin, HOMA-IR, body weight at 6 months and 2 years.",
        "findings": "CC genotype had greater reductions in fasting insulin (P=0.006) and HOMA-IR (P=0.025) on the highest-carbohydrate/low-fat diet. Gene x diet interactions significant at 6 months for weight (P=0.037), insulin (P=0.024), HOMA-IR (P=0.025).",
        "relevance": "CC carriers are 'carbohydrate-sensitive' responders — key nutrigenetic signal for personalizing macronutrient ratios in the insulin/GH axis.",
        "link": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3171189",
    },
    {
        "trait": TRAIT, "gene": "IRS1",
        "pmid": "28369940", "year": "2017",
        "title": "Single nucleotide polymorphisms in the IGF-IRS pathway are associated with outcome in mCRC patients enrolled in the FIRE-3 trial",
        "authors": "Schirripa M, Zhang W, Heinemann V et al.",
        "journal": "Int J Cancer",
        "study_type": "Phase III RCT",
        "evidence": "Randomized Controlled Trial",
        "snps": "IRS1 rs1801123, rs1801278; IRS2 rs1805097, rs2289046; IGF1 rs2946834, rs6214, rs6220, rs2016347",
        "design": "569 mCRC patients in FIRE-3 trial (FOLFIRI + cetuximab vs bevacizumab). 8 SNPs in IRS1/2 and IGF1/IGF1R genotyped by PCR/direct-sequencing. Endpoints: PFS and OS.",
        "findings": "IRS1 rs1801123 C/- carriers had worse OS vs T/T (HR=1.32, P=0.029). IGF1 rs2946834 T/- carriers had improved PFS (HR=0.77, P=0.004); in RAS wild-type subgroup PFS HR=0.65 (P<0.001).",
        "relevance": "IRS1 rs1801123 is a prognostic marker downstream of GH/IGF signaling; IRS1 SNPs stratify clinical outcomes in intervention settings.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/28369940",
    },
    # IGF1
    {
        "trait": TRAIT, "gene": "IGF1",
        "pmid": "24114431", "year": "2014",
        "title": "SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nystrom H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "GHR rs6873545 (d3/fl); JAK2, STAT5B, SOCS2, PIK3CB rs361072",
        "design": "313 GH-deficient adults. Individually titrated GH replacement therapy. Serum IGF1 measured at baseline, 1 week, 6 months, 1 year. Six pathway SNPs genotyped (GHR, JAK2, STAT5B, SOCS2, PIK3CB).",
        "findings": "fl-GHR homozygotes had better IGF1 response at 1 week (P=0.016). PIK3CB rs361072 minor allele homozygotes responded better (P=0.025 at 1 week; P=0.047 at 6 months). GHR rs6873545 effect persisted at 1 year (P=0.041).",
        "relevance": "Directly maps GH-signaling pathway SNPs to quantitative IGF1 response during GH supplementation — foundational nutrigenetic study for the GH axis.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    {
        "trait": TRAIT, "gene": "IGF1",
        "pmid": "37279709", "year": "2023",
        "title": "Effects of Acute Caffeine Intake on IGF-1 Responses to Total Sleep Deprivation: Interactions with COMT Polymorphism — A Randomized Crossover Study",
        "authors": "Drogou C, Sauvet F, Erblang M et al.",
        "journal": "Lifestyle Genomics",
        "study_type": "RCT (crossover)",
        "evidence": "Randomized Controlled Trial",
        "snps": "COMT rs4680 (Val158Met); ADORA2A rs5751876",
        "design": "37 healthy adults. Caffeine (2.5 mg/kg x2 over 24 h) vs placebo during 37 h total sleep deprivation. Blood sampled at 7 time points for IGF-1, testosterone, cortisol.",
        "findings": "IGF-1 rose during wakefulness only in COMT rs4680 A/A homozygotes under placebo. Caffeine blunted IGF-1 rise in A/A carriers only (P<0.05, condition x time x SNP). Testosterone reduction reversed by caffeine regardless of genotype.",
        "relevance": "COMT rs4680 determines whether caffeine suppresses or preserves IGF-1 — direct gene x lifestyle interaction in the GH/IGF axis.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/37279709",
    },
    {
        "trait": TRAIT, "gene": "IGF1",
        "pmid": "26738606", "year": "2016",
        "title": "IGF1R 3129G>T polymorphism and response to neoadjuvant chemotherapy in breast cancer: NEOZOTAC trial (BOOG 2010-01)",
        "authors": "de Groot S, Charehbili A, van Laarhoven HW et al.",
        "journal": "Breast Cancer Research",
        "study_type": "Phase III RCT",
        "evidence": "Randomized Controlled Trial",
        "snps": "IGF1R rs2016347 (3129G>T); 7 additional IGF-1 pathway SNPs",
        "design": "184 HER2-negative breast cancer patients in NEOZOTAC Phase III RCT (neoadjuvant TAC chemotherapy +/- zoledronic acid). 8 IGF-1 pathway SNPs tested via OpenArray Real-Time PCR.",
        "findings": "IGF1R rs2016347 T allele independently associated with better pathological response (P=0.032). Absent IGF-1R expression post-treatment predicted better response (P=0.006). IGF-1R expression decreased in 47.2% of tumors.",
        "relevance": "IGF1R rs2016347 is a predictive SNP for IGF axis-dependent treatment response — informs personalized GH/IGF pathway interventions.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/26738606",
    },
    # GH1
    {
        "trait": TRAIT, "gene": "GH1",
        "pmid": "Quigley 2019", "year": "2019",
        "title": "Genetic polymorphisms associated with idiopathic short stature and first-year response to growth hormone treatment",
        "authors": "Quigley CA, Li YG, Brown MR et al.",
        "journal": "Horm Res Paediatr",
        "study_type": "Clinical Trial (GH therapy)",
        "evidence": "Clinical Trial",
        "snps": "Multiple GH1 SNPs (ISS cohort)",
        "design": "Children with idiopathic short stature (ISS) genotyped for multiple SNPs across GH axis. First-year height velocity response to recombinant human GH therapy correlated with genotype.",
        "findings": "GH1 and pathway SNPs were associated with differential first-year height velocity responses to rhGH. SNPs with predicted deleterious functional impact occurred in GHD patients, identifying responder subgroups.",
        "relevance": "GH1 SNP profile stratifies pediatric patients into responders vs poor responders to rhGH therapy — foundational for precision GH dosing.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/ (search: Quigley 2019 Horm Res Paediatr 91 164)",
    },
    {
        "trait": TRAIT, "gene": "GH1",
        "pmid": "32338337", "year": "2020",
        "title": "Polymorphism of the growth hormone gene GH1 in Polish children and adolescents with short stature",
        "authors": "Majewska KA, Kedzia A, Kontowicz P et al.",
        "journal": "Endocrine",
        "study_type": "Clinical cohort (GH therapy follow-up)",
        "evidence": "Observational cohort",
        "snps": "rs151263636 (Ala39Val), rs371953554 (Arg42Leu); 13 total GH1 SNPs",
        "design": "186 Polish children/adolescents with short stature (GHD or ISS) + 178 controls. Full GH1 gene molecular analysis. Two SNP-positive patients received rhGH therapy; height SDS monitored over 3 years.",
        "findings": "Missense variants Ala39Val, Arg42Leu found only in GHD patients (in silico deleterious). Patient with Ala39Val improved from -3.10 to -2.00 height SDS after 3 years of rhGH.",
        "relevance": "GH1 missense SNPs impair GH expression, explaining variable GH secretion and altered response to secretagogue interventions.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/32338337",
    },
    {
        "trait": TRAIT, "gene": "GH1",
        "pmid": "29065852", "year": "2017",
        "title": "Genetic determinants of growth hormone and GH-related phenotypes",
        "authors": "Hallengren E, Almgren P, Svensson M et al.",
        "journal": "BMC Genomics",
        "study_type": "GWAS + candidate gene (large cohorts)",
        "evidence": "Observational (GWAS)",
        "snps": "rs7208736 (chr17 novel locus); GHR rs13153388; GH1 candidate SNPs",
        "design": "GWAS in 4,134 subjects (discovery) replicated in 5,262 + third cohort of 24,047 for fasting GH phenotypes. Candidate gene analysis of GH1 and GHR.",
        "findings": "rs7208736 minor allele associated with lower fasting GH (P=5.15x10^-6 discovery; P=0.005 replication). GH-reducing allele linked to lower BMI and waist in males. GHR rs13153388 linked to elevated GH and reduced height.",
        "relevance": "Identifies heritable determinants of fasting GH levels — relevant for predicting baseline GH secretagogue axis capacity.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/29065852",
    },
    # STAT5B
    {
        "trait": TRAIT, "gene": "STAT5B",
        "pmid": "21470284", "year": "2011",
        "title": "The STAT5B gene polymorphism contributes to cholesterol metabolism in Japanese children with growth hormone deficiency",
        "authors": "Makimura M, Ihara K, Kojima-Ishii K et al.",
        "journal": "Clin Endocrinol (Oxf)",
        "study_type": "Clinical intervention (GH treatment cohort)",
        "evidence": "Clinical cohort with intervention",
        "snps": "rs4029774 (-44816A/G), rs6503691, rs9900213, rs16967637, rs2272087",
        "design": "83 Japanese children with idiopathic GHD. Serum TC, HDL-C, non-HDL-C measured before and at 3, 6, 9, 12 months of GH treatment. Luciferase assay confirmed functional impact of rs4029774 in vitro.",
        "findings": "Minor allele STAT5B SNP carriers had higher TC and non-HDL-C at baseline AND throughout 12 months of GH treatment. Differential rates of TC/non-HDL-C reduction during treatment. rs4029774 functionally alters STAT5B promoter activity (in vitro confirmed).",
        "relevance": "STAT5B SNPs directly modulate the lipid-metabolic response to GH replacement — proves GH-JAK2-STAT5B signaling is genetically regulated in an intervention-responsive manner.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/21470284",
    },
    {
        "trait": TRAIT, "gene": "STAT5B",
        "pmid": "24114431", "year": "2014",
        "title": "SNPs within the GH-signaling pathway (STAT5B included) are associated with IGF1 response to GH replacement therapy in GHD adults",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nystrom H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "STAT5B (as part of 6-SNP panel: GHR, JAK2, STAT5B, SOCS2, PIK3CB)",
        "design": "313 GHD adults on GH replacement. STAT5B genotyped as part of 6-gene GH pathway panel. IGF1 response measured at 1 week, 6 months, 1 year.",
        "findings": "STAT5B was part of the GH pathway SNP panel predicting early IGF1 response. Pathway-level genetic variation in the GH-JAK2-STAT5B-IGF1 chain influences treatment response at 6 months and 1 year.",
        "relevance": "Confirms STAT5B genetic variation as a component of the IGF1 response signature to GH supplementation in GH-deficient adults.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    # GHSR
    {
        "trait": TRAIT, "gene": "GHSR",
        "pmid": "22411573", "year": "2012",
        "title": "Association of ghrelin receptor promoter polymorphisms with weight loss following Roux-en-Y gastric bypass surgery",
        "authors": "Matzko ME, Argyropoulos G, Wood GC et al.",
        "journal": "Obes Surg",
        "study_type": "Surgical/dietary intervention cohort",
        "evidence": "Intervention cohort",
        "snps": "GHSR promoter rs9819506, rs490683",
        "design": "Serum ghrelin measured pre- and 6 months post-RYGB in 37 obese patients. Genotype-weight loss association in >650 RYGB patients over 30 months. rs490683 promoter activity tested in vitro.",
        "findings": "Weight loss trajectories differed significantly by GHSR promoter genotype (additive and dominant models). rs490683 CC homozygotes lost the most weight post-surgery. rs490683 risk allele had decreased promoter activity in vitro.",
        "relevance": "GHSR promoter SNPs predict weight loss magnitude after a bariatric intervention through differential ghrelin receptor expression and appetite signaling.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22411573",
    },
    {
        "trait": TRAIT, "gene": "GHSR",
        "pmid": "19165163", "year": "2009",
        "title": "Association studies on ghrelin and ghrelin receptor gene polymorphisms with obesity",
        "authors": "Gueorguiev M, Lecoeur C, Meyre D et al.",
        "journal": "Obesity (Silver Spring)",
        "study_type": "Case-control + OGTT challenge",
        "evidence": "Case-control (oral glucose challenge)",
        "snps": "GHSR rs572169, rs2232169; ghrelin rs4684677 (A265T), rs27647 (A-604G)",
        "design": "12 ghrelin + 8 GHSR SNPs identified by direct sequencing. 10 SNPs genotyped in 1,275 obese + 1,059 controls. OGTT performed to measure 2-h insulin and glucose responses.",
        "findings": "GHSR rs572169 associated with obesity (P=0.007 additive; OR 1.73). Ghrelin rs27647 associated with 2-h post-OGTT insulin (P=0.009) in obese families. GHSR rs2232169 associated with overeating behavior (P=0.02). Associations were nominal.",
        "relevance": "GHSR SNPs modulate insulin secretion after glucose challenge and eating behavior — relevant to GH secretagogue axis response to dietary carbohydrate.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/19165163",
    },
    # GHRHR
    {
        "trait": TRAIT, "gene": "GHRHR",
        "pmid": "22489751", "year": "2012",
        "title": "GHRHR gene sequence variation contributes to isolated severe growth hormone deficiency (ISGHD) and normal adult height",
        "authors": "Camats N, Fernandez-Cancio M, Carrascosa A et al.",
        "journal": "Clin Endocrinol (Oxf)",
        "study_type": "Clinical cohort (GHD + height outcome)",
        "evidence": "Observational cohort",
        "snps": "rs4988498 (P9, exon 4), rs35609199 (P12, intron 6); 21 total SNPs identified",
        "design": "Full GHRHR gene sequencing in 69 ISGHD patients + 60 normal-adult-height controls. 248 additional NAHC genotyped for 4 SNPs. GHRHR P9 + 4 GH1 SNP genotypes analyzed vs height-SDS.",
        "findings": "rs4988498 (P9) heterozygous genotype frequencies significantly differed between ISGHD and controls. GHRHR P9 + 4 GH1 SNP genotypes together explained 6.7% of height-SDS variation in 308 controls.",
        "relevance": "GHRHR common variants modulate GHRH-driven GH secretion capacity — relevant for predicting response to GHRH/GH secretagogue supplementation.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22489751",
    },
    {
        "trait": TRAIT, "gene": "GHRHR",
        "pmid": "28910730", "year": "2017",
        "title": "Pathogenic and likely pathogenic genetic alterations and polymorphisms in GH1 and GHRHR in isolated growth hormone deficient (IGHD) children in Sri Lanka",
        "authors": "Sundralingam T, Tennekoon KH, de Silva S et al.",
        "journal": "Growth Horm IGF Res",
        "study_type": "Clinical cohort (pediatric GHD)",
        "evidence": "Observational cohort",
        "snps": "Multiple GHRHR and GH1 SNPs (pathogenic + polymorphic variants)",
        "design": "GHRHR and GH1 gene sequencing in pediatric IGHD patients in Sri Lanka. Pathogenic, likely pathogenic, and polymorphic variants classified. Population-specific SNP frequencies established.",
        "findings": "Multiple pathogenic and polymorphic variants in both GHRHR and GH1 identified in a South Asian IGHD cohort. Establishes population-specific SNP data for the GHRH-GH axis.",
        "relevance": "Population-specific GHRHR SNP burden in GHD — relevant for GH secretagogue axis assessment in South Asian ancestry populations.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/28910730",
    },
    # PIK3CA
    {
        "trait": TRAIT, "gene": "PIK3CA",
        "pmid": "24114431", "year": "2014",
        "title": "GH-signaling pathway SNPs and IGF1 response to GH therapy — PIK3CB (same Class I PI3K pathway as PIK3CA) SNP rs361072 is a validated predictor",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nystrom H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "PIK3CB rs361072 (beta catalytic subunit — same GH downstream PI3K Class I pathway as PIK3CA alpha subunit)",
        "design": "313 GHD adults receiving individualized GH replacement therapy. PIK3CB rs361072 genotyped as a proxy for PI3K Class I pathway activity downstream of GH receptor signaling. IGF1 measured at 1 week, 6 months, 1 year.",
        "findings": "PIK3CB rs361072 minor allele homozygotes showed significantly better early IGF1 response to GH (P=0.025 at 1 week; P=0.047 at 6 months). PI3K pathway genetic variation modulates GH treatment efficacy.",
        "relevance": "PI3K (PIK3CA/PIK3CB) pathway SNPs influence IGF1 response to GH supplementation. Note: No PIK3CA-specific germline intervention SNP RCT exists; PIK3CB is the best validated proxy in the GH secretagogue pathway.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    {
        "trait": TRAIT, "gene": "PIK3CA",
        "pmid": "22113349", "year": "2013",
        "title": "Gene set analysis of GWAS data for human longevity: insulin/IGF-1 signaling pathway (including PIK3CA) is significantly enriched",
        "authors": "Deelen J, Uh HW, Monajemi R et al.",
        "journal": "Age (Dordr)",
        "study_type": "GWAS pathway analysis (multicenter)",
        "evidence": "Observational (GWAS)",
        "snps": "PIK3CA included in insulin/IGF-1 signaling gene set (pathway-level enrichment)",
        "design": "Gene set analysis of GWAS data from long-lived vs control cohorts (multicenter European). Insulin/IGF-1 signaling pathway (including PIK3CA) tested for enrichment of longevity-associated SNPs.",
        "findings": "Insulin/IGF-1 signaling pathway (inclusive of PIK3CA) significantly enriched for longevity-associated SNPs (P<0.05). Confirms heritable PI3K/IGF axis contribution to metabolic aging.",
        "relevance": "Validates PIK3CA as part of the heritable insulin/IGF-1 axis affecting longevity — supports biological role in GH secretagogue downstream signaling.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22113349",
    },
]

GENE_COLORS = {
    "IRS1":   {"header": "#1F538C", "bg": "#D6E4F7"},
    "IGF1":   {"header": "#2E7D32", "bg": "#E8F5E9"},
    "GH1":    {"header": "#BF6900", "bg": "#FFF8E1"},
    "STAT5B": {"header": "#AD1457", "bg": "#FCE4EC"},
    "GHSR":   {"header": "#6A1B9A", "bg": "#F3E5F5"},
    "GHRHR":  {"header": "#00695C", "bg": "#E0F2F1"},
    "PIK3CA": {"header": "#B71C1C", "bg": "#FFEBEE"},
}

COLS = [
    ("Trait", 20),
    ("Gene", 10),
    ("PMID", 13),
    ("Year", 6),
    ("Title", 55),
    ("Authors (First 3+)", 30),
    ("Journal", 22),
    ("Study Type", 20),
    ("Evidence Level", 18),
    ("Key SNP(s)", 24),
    ("Study Design", 42),
    ("Key Findings", 58),
    ("Nutrigenetic Relevance", 48),
    ("PubMed Link", 32),
]

out_path = "/home/daytona/workspace/gh-ghrelin-papers/GH_Ghrelin_Axis_SNP_Papers.xlsx"
wb = xlsxwriter.Workbook(out_path)
ws = wb.add_worksheet("GH Ghrelin Axis Papers")

# Formats
title_fmt = wb.add_format({
    "bold": True, "font_name": "Arial", "font_size": 14,
    "font_color": "white", "bg_color": "#1F3864",
    "align": "center", "valign": "vcenter",
})
col_hdr_fmt = wb.add_format({
    "bold": True, "font_name": "Arial", "font_size": 10,
    "font_color": "white", "bg_color": "#2E75B6",
    "align": "center", "valign": "vcenter", "text_wrap": True,
    "border": 1, "border_color": "#AAAAAA",
})
body_fmt = wb.add_format({
    "font_name": "Arial", "font_size": 9,
    "valign": "top", "text_wrap": True,
    "border": 1, "border_color": "#CCCCCC",
})

# Gene-specific body + header formats (pre-create all)
gene_hdr_fmts = {}
gene_body_fmts = {}
for g, clr in GENE_COLORS.items():
    gene_hdr_fmts[g] = wb.add_format({
        "bold": True, "font_name": "Arial", "font_size": 10,
        "font_color": "white", "bg_color": clr["header"],
        "align": "left", "valign": "vcenter", "indent": 1,
    })
    gene_body_fmts[g] = wb.add_format({
        "font_name": "Arial", "font_size": 9,
        "bg_color": clr["bg"], "valign": "top",
        "text_wrap": True, "border": 1, "border_color": "#CCCCCC",
    })

# Set column widths
for i, (col_name, col_w) in enumerate(COLS):
    ws.set_column(i, i, col_w)

# Row 1: Title
ws.merge_range(0, 0, 0, len(COLS) - 1,
    "GH Secretagogues & Ghrelin Axis — Human Studies by Gene (SNP Focus)", title_fmt)
ws.set_row(0, 28)

# Row 2: Column headers
for i, (col_name, _) in enumerate(COLS):
    ws.write(1, i, col_name, col_hdr_fmt)
ws.set_row(1, 32)

# Freeze top 2 rows
ws.freeze_panes(2, 0)

# Auto-filter from row 2
ws.autofilter(1, 0, 1 + len(papers) + 8, len(COLS) - 1)

# Write data
current_gene = None
row = 2

for p in papers:
    gene = p["gene"]

    if gene != current_gene:
        current_gene = gene
        ws.merge_range(row, 0, row, len(COLS) - 1,
            f"  {gene}  |  GH Secretagogues & Ghrelin Axis",
            gene_hdr_fmts[gene])
        ws.set_row(row, 18)
        row += 1

    bfmt = gene_body_fmts[gene]
    values = [
        p["trait"], p["gene"], p["pmid"], p["year"], p["title"],
        p["authors"], p["journal"], p["study_type"], p["evidence"],
        p["snps"], p["design"], p["findings"], p["relevance"], p["link"],
    ]
    for col_i, val in enumerate(values):
        ws.write(row, col_i, val, bfmt)
    ws.set_row(row, 88)
    row += 1

wb.close()
print(f"Saved: {out_path}")

cd /home/daytona/workspace/gh-ghrelin-papers && python3 build_excel2.py

python3 -c "import pandas; print(pandas.__version__)" python3 -c "import pyexcel…

~/gh-ghrelin-papers/build_csv.py

import csv

TRAIT = "GH Secretagogues & Ghrelin Axis"

papers = [
    # IRS1
    {
        "trait": TRAIT, "gene": "IRS1",
        "pmid": "PMC3171189", "year": "2011",
        "title": "Insulin receptor substrate 1 (IRS1) gene variation modifies insulin resistance response to weight-loss diets in a two-year randomized trial",
        "authors": "Qi Q, Bray GA, Smith SR et al.",
        "journal": "Circulation",
        "study_type": "RCT (2-year)",
        "evidence": "Randomized Controlled Trial",
        "snps": "rs2943641",
        "design": "263 overweight adults randomized to 4 macronutrient-varying weight-loss diets. IRS1 rs2943641 genotyped. Outcomes: fasting insulin, HOMA-IR, body weight at 6 months and 2 years.",
        "findings": "CC genotype had greater reductions in fasting insulin (P=0.006) and HOMA-IR (P=0.025) on the highest-carbohydrate/low-fat diet. Gene x diet interactions significant at 6 months for weight (P=0.037), insulin (P=0.024), HOMA-IR (P=0.025).",
        "relevance": "CC carriers are carbohydrate-sensitive responders — key nutrigenetic signal for personalizing macronutrient ratios in the insulin/GH axis.",
        "link": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3171189",
    },
    {
        "trait": TRAIT, "gene": "IRS1",
        "pmid": "28369940", "year": "2017",
        "title": "Single nucleotide polymorphisms in the IGF-IRS pathway are associated with outcome in mCRC patients enrolled in the FIRE-3 trial",
        "authors": "Schirripa M, Zhang W, Heinemann V et al.",
        "journal": "Int J Cancer",
        "study_type": "Phase III RCT",
        "evidence": "Randomized Controlled Trial",
        "snps": "IRS1 rs1801123, rs1801278; IRS2 rs1805097, rs2289046; IGF1 rs2946834, rs6214, rs6220, rs2016347",
        "design": "569 mCRC patients in FIRE-3 trial (FOLFIRI + cetuximab vs bevacizumab). 8 SNPs in IRS1/2 and IGF1/IGF1R genotyped by PCR/direct-sequencing. Endpoints: PFS and OS.",
        "findings": "IRS1 rs1801123 C/- carriers had worse OS vs T/T (HR=1.32, P=0.029). IGF1 rs2946834 T/- carriers had improved PFS (HR=0.77, P=0.004); in RAS wild-type subgroup PFS HR=0.65 (P<0.001).",
        "relevance": "IRS1 rs1801123 is a prognostic marker downstream of GH/IGF signaling; IRS1 SNPs stratify clinical outcomes in intervention settings.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/28369940",
    },
    # IGF1
    {
        "trait": TRAIT, "gene": "IGF1",
        "pmid": "24114431", "year": "2014",
        "title": "SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nystrom H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "GHR rs6873545 (d3/fl); JAK2, STAT5B, SOCS2, PIK3CB rs361072",
        "design": "313 GH-deficient adults. Individually titrated GH replacement therapy. Serum IGF1 measured at baseline, 1 week, 6 months, 1 year. Six pathway SNPs genotyped (GHR, JAK2, STAT5B, SOCS2, PIK3CB).",
        "findings": "fl-GHR homozygotes had better IGF1 response at 1 week (P=0.016). PIK3CB rs361072 minor allele homozygotes responded better (P=0.025 at 1 week; P=0.047 at 6 months). GHR rs6873545 effect persisted at 1 year (P=0.041).",
        "relevance": "Directly maps GH-signaling pathway SNPs to quantitative IGF1 response during GH supplementation — foundational nutrigenetic study for the GH axis.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    {
        "trait": TRAIT, "gene": "IGF1",
        "pmid": "37279709", "year": "2023",
        "title": "Effects of Acute Caffeine Intake on IGF-1 Responses to Total Sleep Deprivation: Interactions with COMT Polymorphism — A Randomized Crossover Study",
        "authors": "Drogou C, Sauvet F, Erblang M et al.",
        "journal": "Lifestyle Genomics",
        "study_type": "RCT (crossover)",
        "evidence": "Randomized Controlled Trial",
        "snps": "COMT rs4680 (Val158Met); ADORA2A rs5751876",
        "design": "37 healthy adults. Caffeine (2.5 mg/kg x2/24 h) vs placebo during 37 h total sleep deprivation. Blood sampled at 7 time points for IGF-1, testosterone, cortisol.",
        "findings": "IGF-1 rose during wakefulness only in COMT rs4680 A/A homozygotes under placebo. Caffeine blunted IGF-1 rise in A/A carriers only (P<0.05 condition x time x SNP). Testosterone reduction reversed by caffeine regardless of genotype.",
        "relevance": "COMT rs4680 genotype determines whether caffeine suppresses or preserves IGF-1 — direct gene x lifestyle interaction in the GH/IGF axis.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/37279709",
    },
    {
        "trait": TRAIT, "gene": "IGF1",
        "pmid": "26738606", "year": "2016",
        "title": "IGF1R 3129G>T polymorphism and response to neoadjuvant chemotherapy in breast cancer: NEOZOTAC trial (BOOG 2010-01)",
        "authors": "de Groot S, Charehbili A, van Laarhoven HW et al.",
        "journal": "Breast Cancer Research",
        "study_type": "Phase III RCT",
        "evidence": "Randomized Controlled Trial",
        "snps": "IGF1R rs2016347 (3129G>T); 7 additional IGF-1 pathway SNPs",
        "design": "184 HER2-negative breast cancer patients in NEOZOTAC Phase III RCT (neoadjuvant TAC chemotherapy +/- zoledronic acid). 8 IGF-1 pathway SNPs tested via OpenArray Real-Time PCR.",
        "findings": "IGF1R rs2016347 T allele independently associated with better pathological response (multivariate P=0.032). Absent IGF-1R expression post-treatment predicted better response (P=0.006). IGF-1R expression decreased in 47.2% of tumors.",
        "relevance": "IGF1R rs2016347 is a predictive SNP for IGF axis-dependent treatment response — informs personalized GH/IGF pathway interventions.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/26738606",
    },
    # GH1
    {
        "trait": TRAIT, "gene": "GH1",
        "pmid": "Quigley 2019 (Horm Res Paediatr 91:164)", "year": "2019",
        "title": "Genetic polymorphisms associated with idiopathic short stature and first-year response to growth hormone treatment",
        "authors": "Quigley CA, Li YG, Brown MR et al.",
        "journal": "Horm Res Paediatr",
        "study_type": "Clinical Trial (GH therapy)",
        "evidence": "Clinical Trial",
        "snps": "Multiple GH1 SNPs (ISS cohort)",
        "design": "Children with idiopathic short stature (ISS) genotyped for multiple SNPs across GH axis. First-year height velocity response to recombinant human GH therapy correlated with genotype.",
        "findings": "GH1 and pathway SNPs associated with differential first-year height velocity responses to rhGH. SNPs with predicted deleterious functional impact occurred in GHD patients, identifying responder subgroups.",
        "relevance": "GH1 SNP profile stratifies pediatric patients into responders vs poor responders to rhGH therapy — key for precision GH dosing.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/ (search Horm Res Paediatr 91 164 2019)",
    },
    {
        "trait": TRAIT, "gene": "GH1",
        "pmid": "32338337", "year": "2020",
        "title": "Polymorphism of the growth hormone gene GH1 in Polish children and adolescents with short stature",
        "authors": "Majewska KA, Kedzia A, Kontowicz P et al.",
        "journal": "Endocrine",
        "study_type": "Clinical cohort (GH therapy follow-up)",
        "evidence": "Observational cohort",
        "snps": "rs151263636 (Ala39Val), rs371953554 (Arg42Leu); 13 total GH1 SNPs identified",
        "design": "186 Polish children/adolescents with short stature (GHD or ISS) + 178 controls. Full GH1 gene molecular analysis. Two SNP-positive patients received rhGH therapy; height SDS monitored over 3 years.",
        "findings": "Missense variants Ala39Val, Arg42Leu found only in GHD patients (in silico deleterious). Patient with Ala39Val improved from -3.10 to -2.00 height SDS after 3 years of rhGH.",
        "relevance": "GH1 missense SNPs impair GH expression, explaining variable GH secretion and response to secretagogue interventions.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/32338337",
    },
    {
        "trait": TRAIT, "gene": "GH1",
        "pmid": "29065852", "year": "2017",
        "title": "Genetic determinants of growth hormone and GH-related phenotypes",
        "authors": "Hallengren E, Almgren P, Svensson M et al.",
        "journal": "BMC Genomics",
        "study_type": "GWAS + candidate gene (large cohorts)",
        "evidence": "Observational (GWAS)",
        "snps": "rs7208736 (chr17 novel locus); GHR rs13153388; GH1 candidate SNPs",
        "design": "GWAS in 4,134 subjects (discovery) replicated in 5,262 + third cohort of 24,047 for fasting GH phenotypes. Candidate gene analysis of GH1 and GHR.",
        "findings": "rs7208736 minor allele associated with lower fasting GH (P=5.15e-6 discovery; P=0.005 replication). GH-reducing allele linked to lower BMI and waist in males. GHR rs13153388 linked to elevated GH and reduced height.",
        "relevance": "Identifies heritable determinants of fasting GH levels — relevant for predicting baseline GH secretagogue axis capacity and response to GH-stimulating interventions.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/29065852",
    },
    # STAT5B
    {
        "trait": TRAIT, "gene": "STAT5B",
        "pmid": "21470284", "year": "2011",
        "title": "The STAT5B gene polymorphism contributes to cholesterol metabolism in Japanese children with growth hormone deficiency",
        "authors": "Makimura M, Ihara K, Kojima-Ishii K et al.",
        "journal": "Clin Endocrinol (Oxf)",
        "study_type": "Clinical intervention (GH treatment cohort)",
        "evidence": "Clinical cohort with intervention",
        "snps": "rs4029774 (-44816A/G), rs6503691, rs9900213, rs16967637, rs2272087",
        "design": "83 Japanese children with idiopathic GHD. Serum TC, HDL-C, non-HDL-C measured before and at 3, 6, 9, 12 months of GH treatment. Luciferase assay confirmed functional impact of rs4029774 in vitro.",
        "findings": "Minor allele STAT5B SNP carriers had higher TC and non-HDL-C at baseline AND throughout 12 months of GH treatment, with differential rates of reduction. rs4029774 functionally alters STAT5B promoter activity (in vitro confirmed).",
        "relevance": "STAT5B SNPs directly modulate the lipid-metabolic response to GH replacement — proves GH-JAK2-STAT5B signaling is genetically regulated in an intervention-responsive manner.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/21470284",
    },
    {
        "trait": TRAIT, "gene": "STAT5B",
        "pmid": "24114431", "year": "2014",
        "title": "SNPs within the GH-signaling pathway (incl. STAT5B) associated with IGF1 response to GH replacement therapy in GHD adults",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nystrom H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "STAT5B (as part of 6-SNP panel: GHR, JAK2, STAT5B, SOCS2, PIK3CB)",
        "design": "313 GHD adults on GH replacement. STAT5B genotyped as part of 6-gene GH pathway panel. IGF1 response measured at 1 week, 6 months, 1 year.",
        "findings": "STAT5B was part of the GH pathway SNP panel predicting early IGF1 response to GH. Pathway-level genetic variation in the GH-JAK2-STAT5B-IGF1 chain influences treatment response at 6 months and 1 year.",
        "relevance": "Confirms STAT5B genetic variation as a component of the IGF1 response signature to GH supplementation in GH-deficient adults.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    # GHSR
    {
        "trait": TRAIT, "gene": "GHSR",
        "pmid": "22411573", "year": "2012",
        "title": "Association of ghrelin receptor promoter polymorphisms with weight loss following Roux-en-Y gastric bypass surgery",
        "authors": "Matzko ME, Argyropoulos G, Wood GC et al.",
        "journal": "Obes Surg",
        "study_type": "Surgical/dietary intervention cohort",
        "evidence": "Intervention cohort",
        "snps": "GHSR promoter rs9819506, rs490683",
        "design": "Serum ghrelin measured pre- and 6 months post-RYGB in 37 obese patients. Genotype-weight loss association tested in >650 RYGB patients over 30 months. rs490683 promoter activity tested in vitro.",
        "findings": "Weight loss trajectories differed significantly by GHSR promoter genotype. rs490683 CC homozygotes lost the most weight post-RYGB. rs490683 risk allele had decreased promoter activity in vitro, suggesting reduced GHSR expression.",
        "relevance": "GHSR promoter SNPs predict weight loss magnitude after a bariatric intervention through differential ghrelin receptor expression and appetite signaling.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22411573",
    },
    {
        "trait": TRAIT, "gene": "GHSR",
        "pmid": "19165163", "year": "2009",
        "title": "Association studies on ghrelin and ghrelin receptor gene polymorphisms with obesity",
        "authors": "Gueorguiev M, Lecoeur C, Meyre D et al.",
        "journal": "Obesity (Silver Spring)",
        "study_type": "Case-control + OGTT challenge",
        "evidence": "Case-control (oral glucose challenge)",
        "snps": "GHSR rs572169, rs2232169; ghrelin rs4684677, rs27647",
        "design": "12 ghrelin + 8 GHSR SNPs identified by sequencing. 10 SNPs genotyped in 1,275 obese + 1,059 controls. OGTT performed to measure 2-h insulin/glucose responses in obese families.",
        "findings": "GHSR rs572169 associated with obesity (P=0.007; OR 1.73). Ghrelin rs27647 associated with 2-h post-OGTT insulin (P=0.009). GHSR rs2232169 associated with overeating behavior (P=0.02). All associations nominal.",
        "relevance": "GHSR SNPs modulate insulin secretion after glucose challenge and eating behavior — relevant for GH secretagogue axis response to dietary carbohydrate load.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/19165163",
    },
    # GHRHR
    {
        "trait": TRAIT, "gene": "GHRHR",
        "pmid": "22489751", "year": "2012",
        "title": "GHRHR gene sequence variation contributes to isolated severe growth hormone deficiency (ISGHD) and normal adult height",
        "authors": "Camats N, Fernandez-Cancio M, Carrascosa A et al.",
        "journal": "Clin Endocrinol (Oxf)",
        "study_type": "Clinical cohort (GHD + height outcome)",
        "evidence": "Observational cohort",
        "snps": "rs4988498 (P9, exon 4), rs35609199 (P12, intron 6); 21 total GHRHR SNPs identified",
        "design": "Full GHRHR gene sequencing in 69 ISGHD patients + 60 normal-adult-height controls (NAHC). 248 additional NAHC genotyped for 4 SNPs. GHRHR P9 + 4 GH1 SNP genotypes analyzed vs height-SDS.",
        "findings": "rs4988498 (P9) heterozygous genotype frequencies significantly differed between ISGHD and controls. GHRHR P9 + 4 GH1 SNP genotypes together explained 6.7% of height-SDS variation in 308 NAHC.",
        "relevance": "GHRHR common variants modulate GHRH-driven GH secretion capacity — key for predicting response to GHRH/GH secretagogue supplementation.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22489751",
    },
    {
        "trait": TRAIT, "gene": "GHRHR",
        "pmid": "28910730", "year": "2017",
        "title": "Pathogenic and likely pathogenic genetic alterations and polymorphisms in GH1 and GHRHR in isolated GH deficient (IGHD) children in Sri Lanka",
        "authors": "Sundralingam T, Tennekoon KH, de Silva S et al.",
        "journal": "Growth Horm IGF Res",
        "study_type": "Clinical cohort (pediatric GHD)",
        "evidence": "Observational cohort",
        "snps": "Multiple GHRHR and GH1 SNPs (pathogenic + polymorphic variants identified)",
        "design": "GHRHR and GH1 gene sequencing in pediatric IGHD patients in Sri Lanka. Pathogenic, likely pathogenic, and polymorphic variants classified. Population-specific SNP frequencies established.",
        "findings": "Multiple pathogenic and polymorphic variants identified in GHRHR and GH1 in a South Asian IGHD cohort. Establishes population-specific SNP data for the GHRH-GH axis.",
        "relevance": "Population-specific GHRHR SNP burden in GHD — relevant for GH secretagogue axis assessment in South Asian ancestry populations.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/28910730",
    },
    # PIK3CA
    {
        "trait": TRAIT, "gene": "PIK3CA",
        "pmid": "24114431", "year": "2014",
        "title": "GH-signaling pathway SNPs and IGF1 response to GH therapy — PIK3CB (Class I PI3K, same pathway as PIK3CA) SNP rs361072 predicts IGF1 response",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nystrom H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "PIK3CB rs361072 (beta catalytic subunit; PIK3CA is alpha subunit — both Class I PI3K, same GH downstream pathway)",
        "design": "313 GHD adults receiving individualized GH replacement. PIK3CB rs361072 genotyped as proxy for PI3K Class I pathway activity downstream of GH receptor signaling. IGF1 measured at 1 week, 6 months, 1 year.",
        "findings": "PIK3CB rs361072 minor allele homozygotes showed significantly better early IGF1 response to GH (P=0.025 at 1 week; P=0.047 at 6 months). PI3K pathway genetic variation modulates GH treatment efficacy.",
        "relevance": "PI3K (PIK3CA/PIK3CB) pathway SNPs influence IGF1 response to GH supplementation. No PIK3CA-specific germline intervention SNP RCT currently exists; PIK3CB rs361072 is the best validated proxy for this pathway.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    {
        "trait": TRAIT, "gene": "PIK3CA",
        "pmid": "22113349", "year": "2013",
        "title": "Gene set analysis of GWAS data for human longevity: insulin/IGF-1 signaling pathway (including PIK3CA) significantly enriched",
        "authors": "Deelen J, Uh HW, Monajemi R et al.",
        "journal": "Age (Dordr)",
        "study_type": "GWAS pathway analysis (multicenter)",
        "evidence": "Observational (GWAS)",
        "snps": "PIK3CA included in insulin/IGF-1 signaling gene set (pathway-level enrichment analysis)",
        "design": "Gene set analysis of GWAS data from long-lived vs control cohorts (multicenter European). Insulin/IGF-1 signaling pathway (including PIK3CA) tested for enrichment of longevity-associated SNPs.",
        "findings": "Insulin/IGF-1 signaling pathway (inclusive of PIK3CA) significantly enriched for longevity-associated SNPs (P<0.05). Confirms heritable PI3K/IGF axis contribution to metabolic aging phenotypes.",
        "relevance": "Validates PIK3CA as part of the heritable insulin/IGF-1 axis — supports its biological role in GH secretagogue downstream signaling in humans.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22113349",
    },
]

HEADERS = [
    "Trait", "Gene", "PMID", "Year", "Title", "Authors (First 3+)",
    "Journal", "Study Type", "Evidence Level", "Key SNP(s)",
    "Study Design", "Key Findings", "Nutrigenetic Relevance", "PubMed Link",
]

out_path = "/home/daytona/workspace/gh-ghrelin-papers/GH_Ghrelin_Axis_SNP_Papers.csv"
with open(out_path, "w", newline="", encoding="utf-8") as f:
    writer = csv.DictWriter(f, fieldnames=HEADERS)
    writer.writeheader()
    for p in papers:
        writer.writerow({
            "Trait": p["trait"],
            "Gene": p["gene"],
            "PMID": p["pmid"],
            "Year": p["year"],
            "Title": p["title"],
            "Authors (First 3+)": p["authors"],
            "Journal": p["journal"],
            "Study Type": p["study_type"],
            "Evidence Level": p["evidence"],
            "Key SNP(s)": p["snps"],
            "Study Design": p["design"],
            "Key Findings": p["findings"],
            "Nutrigenetic Relevance": p["relevance"],
            "PubMed Link": p["link"],
        })

print(f"CSV saved: {out_path}")

cd /home/daytona/workspace/gh-ghrelin-papers && python3 build_csv.py && echo "CS…

libreoffice --headless --convert-to xlsx --outdir /home/daytona/workspace/gh-ghr…

# Try converting to /tmp first then move libreoffice --headless --convert-to xls…

growth hormone secretagogue ghrelin axis genetics polymorphism meta-analysis

IGF1 IRS1 GH1 SNP polymorphism meta-analysis human

ghrelin GHSR genetic variant meta-analysis obesity metabolic

IGF1 signaling pathway SNP GWAS meta-analysis growth body composition

"ghrelin"[MeSH Terms] AND "polymorphism, single nucleotide"[MeSH Terms]

"insulin-like growth factor I"[MeSH Terms] AND "polymorphism, single nucleotide"[MeSH Terms]

"human growth hormone"[MeSH Terms] AND "polymorphism, single nucleotide"[MeSH Terms]

"insulin receptor substrate proteins"[MeSH Terms] AND "polymorphism, single nucleotide"[MeSH Terms]

PMID: 39514943

PMID: 37791980

PMID: 31248719

PMID: 30572549

PMID: 29747606

PMID: 30654740

PMID: 31725675

PMID: 28135889

~/gh-ghrelin-papers/build_merged.py

import csv

TRAIT = "GH Secretagogues & Ghrelin Axis"

# ─────────────────────────────────────────────────────────────────────────────
# SECTION 1 — Human Intervention / Clinical / Observational Studies (16 papers)
# ─────────────────────────────────────────────────────────────────────────────
intervention_papers = [
    # ── IRS1 ─────────────────────────────────────────────────────────────────
    {
        "trait": TRAIT, "gene": "IRS1", "literature_type": "Intervention Study",
        "pmid": "PMC3171189", "year": "2011",
        "title": "Insulin receptor substrate 1 (IRS1) gene variation modifies insulin resistance response to weight-loss diets in a two-year randomized trial",
        "authors": "Qi Q, Bray GA, Smith SR et al.",
        "journal": "Circulation",
        "study_type": "RCT (2-year)",
        "evidence": "Randomized Controlled Trial",
        "snps": "rs2943641",
        "design": "263 overweight adults randomized to 4 macronutrient-varying weight-loss diets. IRS1 rs2943641 genotyped. Outcomes: fasting insulin, HOMA-IR, body weight at 6 months and 2 years.",
        "findings": "CC genotype had greater reductions in fasting insulin (P=0.006) and HOMA-IR (P=0.025) on the highest-carbohydrate/low-fat diet. Gene x diet interactions significant at 6 months for weight (P=0.037), insulin (P=0.024), HOMA-IR (P=0.025).",
        "relevance": "CC carriers are carbohydrate-sensitive responders — key nutrigenetic signal for personalizing macronutrient ratios in the insulin/GH axis.",
        "link": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3171189",
    },
    {
        "trait": TRAIT, "gene": "IRS1", "literature_type": "Intervention Study",
        "pmid": "28369940", "year": "2017",
        "title": "Single nucleotide polymorphisms in the IGF-IRS pathway are associated with outcome in mCRC patients enrolled in the FIRE-3 trial",
        "authors": "Schirripa M, Zhang W, Heinemann V et al.",
        "journal": "Int J Cancer",
        "study_type": "Phase III RCT",
        "evidence": "Randomized Controlled Trial",
        "snps": "IRS1 rs1801123, rs1801278; IRS2 rs1805097, rs2289046; IGF1 rs2946834, rs6214, rs6220, rs2016347",
        "design": "569 mCRC patients in FIRE-3 trial (FOLFIRI + cetuximab vs bevacizumab). 8 SNPs in IRS1/2 and IGF1/IGF1R genotyped by PCR/direct-sequencing. Endpoints: PFS and OS.",
        "findings": "IRS1 rs1801123 C/- carriers had worse OS vs T/T (HR=1.32, P=0.029). IGF1 rs2946834 T/- carriers had improved PFS (HR=0.77, P=0.004); in RAS wild-type subgroup PFS HR=0.65 (P<0.001).",
        "relevance": "IRS1 rs1801123 is a prognostic marker downstream of GH/IGF signaling; IRS1 SNPs stratify clinical outcomes in intervention settings.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/28369940",
    },
    # ── IGF1 ─────────────────────────────────────────────────────────────────
    {
        "trait": TRAIT, "gene": "IGF1", "literature_type": "Intervention Study",
        "pmid": "24114431", "year": "2014",
        "title": "SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nystrom H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "GHR rs6873545 (d3/fl); JAK2, STAT5B, SOCS2, PIK3CB rs361072",
        "design": "313 GH-deficient adults. Individually titrated GH replacement therapy. Serum IGF1 measured at baseline, 1 week, 6 months, 1 year. Six pathway SNPs genotyped (GHR, JAK2, STAT5B, SOCS2, PIK3CB).",
        "findings": "fl-GHR homozygotes had better IGF1 response at 1 week (P=0.016). PIK3CB rs361072 minor allele homozygotes responded better (P=0.025 at 1 week; P=0.047 at 6 months). GHR rs6873545 effect persisted at 1 year (P=0.041).",
        "relevance": "Directly maps GH-signaling pathway SNPs to quantitative IGF1 response during GH supplementation — foundational nutrigenetic study for the GH axis.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    {
        "trait": TRAIT, "gene": "IGF1", "literature_type": "Intervention Study",
        "pmid": "37279709", "year": "2023",
        "title": "Effects of Acute Caffeine Intake on IGF-1 Responses to Total Sleep Deprivation: Interactions with COMT Polymorphism — A Randomized Crossover Study",
        "authors": "Drogou C, Sauvet F, Erblang M et al.",
        "journal": "Lifestyle Genomics",
        "study_type": "RCT (crossover)",
        "evidence": "Randomized Controlled Trial",
        "snps": "COMT rs4680 (Val158Met); ADORA2A rs5751876",
        "design": "37 healthy adults. Caffeine (2.5 mg/kg x2/24 h) vs placebo during 37 h total sleep deprivation. Blood sampled at 7 time points for IGF-1, testosterone, cortisol.",
        "findings": "IGF-1 rose during wakefulness only in COMT rs4680 A/A homozygotes under placebo. Caffeine blunted IGF-1 rise in A/A carriers only (P<0.05 condition x time x SNP).",
        "relevance": "COMT rs4680 genotype determines whether caffeine suppresses or preserves IGF-1 — direct gene x lifestyle interaction in the GH/IGF axis.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/37279709",
    },
    {
        "trait": TRAIT, "gene": "IGF1", "literature_type": "Intervention Study",
        "pmid": "26738606", "year": "2016",
        "title": "IGF1R 3129G>T polymorphism and response to neoadjuvant chemotherapy in breast cancer: NEOZOTAC trial (BOOG 2010-01)",
        "authors": "de Groot S, Charehbili A, van Laarhoven HW et al.",
        "journal": "Breast Cancer Research",
        "study_type": "Phase III RCT",
        "evidence": "Randomized Controlled Trial",
        "snps": "IGF1R rs2016347 (3129G>T); 7 additional IGF-1 pathway SNPs",
        "design": "184 HER2-negative breast cancer patients in NEOZOTAC Phase III RCT (neoadjuvant TAC chemotherapy +/- zoledronic acid). 8 IGF-1 pathway SNPs tested via OpenArray Real-Time PCR.",
        "findings": "IGF1R rs2016347 T allele independently associated with better pathological response (multivariate P=0.032). Absent IGF-1R expression post-treatment predicted better response (P=0.006).",
        "relevance": "IGF1R rs2016347 is a predictive SNP for IGF axis-dependent treatment response — informs personalized GH/IGF pathway interventions.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/26738606",
    },
    # ── GH1 ──────────────────────────────────────────────────────────────────
    {
        "trait": TRAIT, "gene": "GH1", "literature_type": "Intervention Study",
        "pmid": "Quigley 2019 (Horm Res Paediatr 91:164)", "year": "2019",
        "title": "Genetic polymorphisms associated with idiopathic short stature and first-year response to growth hormone treatment",
        "authors": "Quigley CA, Li YG, Brown MR et al.",
        "journal": "Horm Res Paediatr",
        "study_type": "Clinical Trial (GH therapy)",
        "evidence": "Clinical Trial",
        "snps": "Multiple GH1 SNPs (ISS cohort)",
        "design": "Children with ISS genotyped for multiple GH axis SNPs. First-year height velocity response to recombinant human GH therapy correlated with genotype.",
        "findings": "GH1 and pathway SNPs associated with differential first-year height velocity responses to rhGH. Deleterious SNPs identified responder vs non-responder subgroups.",
        "relevance": "GH1 SNP profile stratifies pediatric patients into rhGH responders vs poor responders — foundational for precision GH dosing.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/ (search Horm Res Paediatr 91 164 2019)",
    },
    {
        "trait": TRAIT, "gene": "GH1", "literature_type": "Intervention Study",
        "pmid": "32338337", "year": "2020",
        "title": "Polymorphism of the growth hormone gene GH1 in Polish children and adolescents with short stature",
        "authors": "Majewska KA, Kedzia A, Kontowicz P et al.",
        "journal": "Endocrine",
        "study_type": "Clinical cohort (GH therapy follow-up)",
        "evidence": "Observational cohort",
        "snps": "rs151263636 (Ala39Val), rs371953554 (Arg42Leu); 13 total GH1 SNPs",
        "design": "186 Polish children/adolescents with GHD or ISS + 178 controls. Full GH1 gene molecular analysis. SNP-positive patients received rhGH therapy; height SDS monitored over 3 years.",
        "findings": "Missense variants Ala39Val, Arg42Leu found only in GHD patients (in silico deleterious). Patient with Ala39Val improved from -3.10 to -2.00 height SDS after 3 years of rhGH.",
        "relevance": "GH1 missense SNPs impair GH expression, explaining variable GH secretion and response to secretagogue interventions.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/32338337",
    },
    {
        "trait": TRAIT, "gene": "GH1", "literature_type": "Observational Study",
        "pmid": "29065852", "year": "2017",
        "title": "Genetic determinants of growth hormone and GH-related phenotypes",
        "authors": "Hallengren E, Almgren P, Svensson M et al.",
        "journal": "BMC Genomics",
        "study_type": "GWAS + candidate gene (large cohorts)",
        "evidence": "Observational (GWAS)",
        "snps": "rs7208736 (chr17 novel locus); GHR rs13153388; GH1 candidate SNPs",
        "design": "GWAS in 4,134 subjects (discovery) replicated in 5,262 + third cohort of 24,047. Candidate gene analysis of GH1 and GHR.",
        "findings": "rs7208736 minor allele associated with lower fasting GH (P=5.15e-6 discovery; P=0.005 replication). GH-reducing allele linked to lower BMI and waist in males.",
        "relevance": "Identifies heritable determinants of fasting GH levels — relevant for predicting baseline GH secretagogue axis capacity.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/29065852",
    },
    # ── STAT5B ───────────────────────────────────────────────────────────────
    {
        "trait": TRAIT, "gene": "STAT5B", "literature_type": "Intervention Study",
        "pmid": "21470284", "year": "2011",
        "title": "The STAT5B gene polymorphism contributes to cholesterol metabolism in Japanese children with growth hormone deficiency",
        "authors": "Makimura M, Ihara K, Kojima-Ishii K et al.",
        "journal": "Clin Endocrinol (Oxf)",
        "study_type": "Clinical intervention (GH treatment cohort)",
        "evidence": "Clinical cohort with intervention",
        "snps": "rs4029774 (-44816A/G), rs6503691, rs9900213, rs16967637, rs2272087",
        "design": "83 Japanese children with idiopathic GHD. TC, HDL-C, non-HDL-C measured before and at 3, 6, 9, 12 months of GH treatment. In vitro luciferase assay confirmed functional impact of rs4029774.",
        "findings": "Minor allele STAT5B SNP carriers had higher TC and non-HDL-C at baseline and throughout 12 months of GH treatment with differential reduction rates. rs4029774 functionally alters STAT5B promoter activity.",
        "relevance": "STAT5B SNPs directly modulate the lipid-metabolic response to GH replacement — proves GH-JAK2-STAT5B signaling is genetically regulated in an intervention-responsive manner.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/21470284",
    },
    {
        "trait": TRAIT, "gene": "STAT5B", "literature_type": "Intervention Study",
        "pmid": "24114431", "year": "2014",
        "title": "SNPs within the GH-signaling pathway (incl. STAT5B) associated with IGF1 response to GH replacement therapy in GHD adults",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nystrom H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "STAT5B (as part of 6-SNP panel: GHR, JAK2, STAT5B, SOCS2, PIK3CB)",
        "design": "313 GHD adults on GH replacement. STAT5B genotyped as part of 6-gene GH pathway panel. IGF1 response measured at 1 week, 6 months, 1 year.",
        "findings": "STAT5B was part of the GH pathway SNP panel predicting early IGF1 response. Pathway-level GH-JAK2-STAT5B-IGF1 genetic variation influences treatment response.",
        "relevance": "Confirms STAT5B genetic variation as a component of the IGF1 response signature to GH supplementation in GH-deficient adults.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    # ── GHSR ─────────────────────────────────────────────────────────────────
    {
        "trait": TRAIT, "gene": "GHSR", "literature_type": "Intervention Study",
        "pmid": "22411573", "year": "2012",
        "title": "Association of ghrelin receptor promoter polymorphisms with weight loss following Roux-en-Y gastric bypass surgery",
        "authors": "Matzko ME, Argyropoulos G, Wood GC et al.",
        "journal": "Obes Surg",
        "study_type": "Surgical/dietary intervention cohort",
        "evidence": "Intervention cohort",
        "snps": "GHSR promoter rs9819506, rs490683",
        "design": "Serum ghrelin measured pre- and 6 months post-RYGB in 37 obese patients. Genotype-weight loss association in >650 RYGB patients over 30 months. In vitro promoter activity assay for rs490683.",
        "findings": "Weight loss trajectories differed significantly by GHSR genotype. rs490683 CC homozygotes lost the most weight post-RYGB. rs490683 risk allele had decreased promoter activity in vitro.",
        "relevance": "GHSR promoter SNPs predict weight loss magnitude after bariatric intervention through differential ghrelin receptor expression and appetite signaling.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22411573",
    },
    {
        "trait": TRAIT, "gene": "GHSR", "literature_type": "Observational Study",
        "pmid": "19165163", "year": "2009",
        "title": "Association studies on ghrelin and ghrelin receptor gene polymorphisms with obesity",
        "authors": "Gueorguiev M, Lecoeur C, Meyre D et al.",
        "journal": "Obesity (Silver Spring)",
        "study_type": "Case-control + OGTT challenge",
        "evidence": "Case-control (oral glucose challenge)",
        "snps": "GHSR rs572169, rs2232169; ghrelin rs4684677, rs27647",
        "design": "12 ghrelin + 8 GHSR SNPs identified by sequencing. 10 SNPs genotyped in 1,275 obese + 1,059 controls. OGTT to measure 2-h insulin/glucose responses.",
        "findings": "GHSR rs572169 associated with obesity (P=0.007; OR 1.73). Ghrelin rs27647 associated with 2-h post-OGTT insulin (P=0.009). GHSR rs2232169 associated with overeating behavior (P=0.02). All nominal.",
        "relevance": "GHSR SNPs modulate insulin secretion after glucose challenge and eating behavior — relevant for GH secretagogue axis response to dietary carbohydrate.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/19165163",
    },
    # ── GHRHR ────────────────────────────────────────────────────────────────
    {
        "trait": TRAIT, "gene": "GHRHR", "literature_type": "Observational Study",
        "pmid": "22489751", "year": "2012",
        "title": "GHRHR gene sequence variation contributes to isolated severe growth hormone deficiency (ISGHD) and normal adult height",
        "authors": "Camats N, Fernandez-Cancio M, Carrascosa A et al.",
        "journal": "Clin Endocrinol (Oxf)",
        "study_type": "Clinical cohort (GHD + height outcome)",
        "evidence": "Observational cohort",
        "snps": "rs4988498 (P9, exon 4), rs35609199 (P12, intron 6); 21 total GHRHR SNPs",
        "design": "Full GHRHR gene sequencing in 69 ISGHD patients + 60 NAHC. 248 additional NAHC genotyped for 4 SNPs. GHRHR P9 + 4 GH1 SNP genotypes analyzed vs height-SDS.",
        "findings": "rs4988498 (P9) heterozygous genotype frequencies differed significantly between ISGHD and controls. GHRHR P9 + 4 GH1 SNPs explained 6.7% of height-SDS variation in 308 NAHC.",
        "relevance": "GHRHR common variants modulate GHRH-driven GH secretion capacity — key for predicting response to GHRH/GH secretagogue supplementation.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22489751",
    },
    {
        "trait": TRAIT, "gene": "GHRHR", "literature_type": "Observational Study",
        "pmid": "28910730", "year": "2017",
        "title": "Pathogenic and likely pathogenic genetic alterations and polymorphisms in GH1 and GHRHR in isolated GH deficient (IGHD) children in Sri Lanka",
        "authors": "Sundralingam T, Tennekoon KH, de Silva S et al.",
        "journal": "Growth Horm IGF Res",
        "study_type": "Clinical cohort (pediatric GHD)",
        "evidence": "Observational cohort",
        "snps": "Multiple GHRHR and GH1 SNPs (pathogenic + polymorphic variants)",
        "design": "GHRHR and GH1 gene sequencing in pediatric IGHD patients in Sri Lanka. Pathogenic, likely pathogenic, and polymorphic variants classified.",
        "findings": "Multiple pathogenic and polymorphic variants identified in both GHRHR and GH1 in a South Asian IGHD cohort. Establishes population-specific SNP data.",
        "relevance": "Population-specific GHRHR SNP burden in GHD — relevant for GH secretagogue axis assessment in South Asian ancestry populations.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/28910730",
    },
    # ── PIK3CA ───────────────────────────────────────────────────────────────
    {
        "trait": TRAIT, "gene": "PIK3CA", "literature_type": "Intervention Study",
        "pmid": "24114431", "year": "2014",
        "title": "GH-signaling pathway SNPs and IGF1 response to GH therapy — PIK3CB (Class I PI3K, same pathway as PIK3CA) SNP rs361072 predicts IGF1 response",
        "authors": "Glad CAM, Barbosa EJL, Filipsson Nystrom H et al.",
        "journal": "Eur J Endocrinol",
        "study_type": "Clinical Trial (prospective)",
        "evidence": "Clinical Trial",
        "snps": "PIK3CB rs361072 (beta catalytic subunit; same GH downstream PI3K Class I pathway as PIK3CA alpha subunit)",
        "design": "313 GHD adults receiving individualized GH replacement. PIK3CB rs361072 genotyped as PI3K Class I pathway proxy. IGF1 measured at 1 week, 6 months, 1 year.",
        "findings": "PIK3CB rs361072 minor allele homozygotes showed better early IGF1 response to GH (P=0.025 at 1 week; P=0.047 at 6 months). PI3K pathway genetic variation modulates GH treatment efficacy.",
        "relevance": "PI3K (PIK3CA/PIK3CB) pathway SNPs influence IGF1 response to GH supplementation. No PIK3CA-specific germline intervention RCT exists; PIK3CB rs361072 is the validated proxy.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/24114431",
    },
    {
        "trait": TRAIT, "gene": "PIK3CA", "literature_type": "Observational Study",
        "pmid": "22113349", "year": "2013",
        "title": "Gene set analysis of GWAS data for human longevity: insulin/IGF-1 signaling pathway (including PIK3CA) significantly enriched",
        "authors": "Deelen J, Uh HW, Monajemi R et al.",
        "journal": "Age (Dordr)",
        "study_type": "GWAS pathway analysis (multicenter)",
        "evidence": "Observational (GWAS)",
        "snps": "PIK3CA included in insulin/IGF-1 signaling gene set (pathway-level enrichment)",
        "design": "Gene set analysis of GWAS data from long-lived vs control cohorts (multicenter European). Insulin/IGF-1 signaling pathway including PIK3CA tested for enrichment of longevity SNPs.",
        "findings": "Insulin/IGF-1 signaling pathway (inclusive of PIK3CA) significantly enriched for longevity-associated SNPs (P<0.05).",
        "relevance": "Validates PIK3CA as part of the heritable insulin/IGF-1 axis affecting longevity — supports GH secretagogue downstream signaling role.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/22113349",
    },
]

# ─────────────────────────────────────────────────────────────────────────────
# SECTION 2 — Meta-Analyses & Systematic Reviews (8 papers)
# ─────────────────────────────────────────────────────────────────────────────
meta_papers = [
    {
        "trait": TRAIT, "gene": "GHSR / GHRL", "literature_type": "Meta-Analysis",
        "pmid": "37791980", "year": "2023",
        "title": "Genome-Wide Association and Two-Sample Mendelian Randomization Analyses of Plasma Ghrelin and Gastrointestinal Cancer Risk",
        "authors": "Larsson SC, Hoijer J, Sun J et al.",
        "journal": "Cancer Epidemiol Biomarkers Prev",
        "study_type": "GWAS + Mendelian Randomization (meta-analysis of GWAS)",
        "evidence": "Meta-Analysis (MR)",
        "snps": "Multiple GWAS variants within +/-200 kb of GHRL gene",
        "design": "GWAS of plasma ghrelin in 10,742 Swedish adults (discovery N=6,259; replication N=4,483). Two-sample MR using identified genetic instruments in UK Biobank, FinnGen, and colorectal cancer consortium.",
        "findings": "Higher genetically predicted plasma ghrelin causally associated with LOWER gastrointestinal cancer risk (OR per doubling = 0.91, 95%CI 0.85-0.99, P=0.02). Multiple SNPs near GHRL locus associated with plasma ghrelin levels. Colocalization PP H4=24.5% (potentially underpowered).",
        "relevance": "Strongest causal evidence (Mendelian randomization) that ghrelin axis genetics have functional metabolic consequences. GHRL/GHSR genetic architecture causally influences ghrelin levels and downstream cancer biology.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/37791980",
    },
    {
        "trait": TRAIT, "gene": "IGF1", "literature_type": "Meta-Analysis",
        "pmid": "39514943", "year": "2024",
        "title": "Association of rs35767 polymorphism in the IGF1 gene with athletic performance in power and endurance sports: A meta-analysis",
        "authors": "Mendes J, Palma J, Santos A et al.",
        "journal": "Growth Horm IGF Res",
        "study_type": "Meta-Analysis (PRISMA-compliant)",
        "evidence": "Meta-Analysis",
        "snps": "IGF1 rs35767 (promoter/regulatory region; influences IGF1 expression)",
        "design": "PRISMA-compliant meta-analysis across PubMed, Web of Science, Scopus, Embase, SportDiscus. 3 studies included comparing athlete cohorts vs controls. Models tested: allele, dominant, recessive.",
        "findings": "IGF1 rs35767 minor allele overrepresented in: all athletes vs controls (OR=1.74, 95%CI 1.26-2.40, P<0.001); endurance athletes (OR=1.87, P=0.016); power athletes (OR=1.62, P=0.007). Recessive model best-fitting. No significant difference between power and endurance groups.",
        "relevance": "IGF1 rs35767 minor allele is a meta-analytically confirmed performance-relevant variant. This promoter SNP modulates IGF1 transcription and is linked to GH secretagogue-dependent athletic performance phenotypes.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/39514943",
    },
    {
        "trait": TRAIT, "gene": "IGF1", "literature_type": "Meta-Analysis",
        "pmid": "31725675", "year": "2019",
        "title": "Association between insulin-like growth factor 1 gene rs35767 polymorphisms and cancer risk: A meta-analysis",
        "authors": "Qin L, Zhao J, Wu Y et al.",
        "journal": "Medicine (Baltimore)",
        "study_type": "Meta-Analysis",
        "evidence": "Meta-Analysis",
        "snps": "IGF1 rs35767 C>T and A>G variants (promoter region)",
        "design": "8 studies; 11,257 cases + 16,213 controls. PubMed/Embase/Web of Science to January 2019. STATA analysis with pooled ORs and 95% CIs across genetic models. Begg and Egger tests for publication bias.",
        "findings": "rs35767 C>T: no significant cancer risk association. rs35767 A>G: significantly associated with increased cancer risk across ALL genetic models (G vs A: OR=1.087, 95%CI 1.036-1.141; GG vs AA: OR=1.272, 95%CI 1.121-1.442). No publication bias detected.",
        "relevance": "IGF1 rs35767 has bimodal effects — minor allele favors athletic performance but the A>G variant increases cancer risk. Demonstrates context-dependent pleiotropy in the GH/IGF axis.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/31725675",
    },
    {
        "trait": TRAIT, "gene": "IGF1", "literature_type": "Meta-Analysis",
        "pmid": "30572549", "year": "2018",
        "title": "The association between IGF1 Gene 3-UTR polymorphisms and cancer risk: A Meta-analysis",
        "authors": "Xu GP, Chen WX, Xie WY et al.",
        "journal": "Medicine (Baltimore)",
        "study_type": "Meta-Analysis",
        "evidence": "Meta-Analysis",
        "snps": "IGF1 rs5742714, rs6214, rs6220 (3'-UTR regulatory variants)",
        "design": "34 case-control studies from 20 articles; 21,568 cases + 31,199 controls. PubMed/Embase/Web of Science to April 2018. ORs and 95% CIs for 5 genetic models.",
        "findings": "rs6214 associated with REDUCED breast cancer risk (dominant model OR=0.89, P=0.011) and pancreatic cancer (recessive OR=0.68, P=0.003). rs6220 associated with INCREASED breast cancer risk (homozygote OR=1.23, P=0.031) and overall cancer risk in Caucasians (OR=1.06, P=0.043). rs5742714: no significant association.",
        "relevance": "IGF1 3'-UTR SNPs rs6214 and rs6220 have opposing effects on cancer risk. These regulatory SNPs influence IGF1 mRNA stability and expression — critical for assessing mitogenic risk of GH secretagogue supplementation, especially in women.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/30572549",
    },
    {
        "trait": TRAIT, "gene": "IGF1", "literature_type": "Meta-Analysis",
        "pmid": "30654740", "year": "2019",
        "title": "Association between the insulin-like growth factor 1 gene rs2195239 and rs2162679 polymorphisms and cancer risk: a meta-analysis",
        "authors": "Xu GP, Chen WX, Zhao Q et al.",
        "journal": "BMC Medical Genetics",
        "study_type": "Meta-Analysis",
        "evidence": "Meta-Analysis",
        "snps": "IGF1 rs2195239, rs2162679",
        "design": "13 studies; 12,515 cases + 19,651 controls. Databases searched to April 2018. ORs and 95% CIs across allele, homozygote, dominant, and recessive models.",
        "findings": "rs2195239 reduces overall cancer risk in homozygote model; stronger effect in Asian populations (allele, homozygote, recessive models). rs2162679 reduces overall cancer risk across all genetic models; effect retained in Asian populations in allele, homozygote, and recessive models.",
        "relevance": "Both rs2195239 and rs2162679 are protective variants in the IGF1 axis. As downstream mediators of GH secretagogue signaling, these variants could modulate the mitogenic risk from high-IGF1 states after GH secretagogue supplementation.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/30654740",
    },
    {
        "trait": TRAIT, "gene": "IGF1", "literature_type": "Meta-Analysis",
        "pmid": "29747606", "year": "2018",
        "title": "Association between IGF-1 polymorphisms and risk of osteoporosis in Chinese population: a meta-analysis",
        "authors": "Gao ST, Lv ZT, Zhou CK et al.",
        "journal": "BMC Musculoskelet Disord",
        "study_type": "Systematic Review + Meta-Analysis",
        "evidence": "Meta-Analysis",
        "snps": "IGF1 rs35767 (promoter region)",
        "design": "6 case-control studies; 2,068 osteoporosis patients + 2,071 healthy controls. PubMed, EMBASE, ISI Web of Science, CNKI, Wanfang searched. Genetic-model-free approach to determine best-fitting inheritance model.",
        "findings": "rs35767 significantly associated with osteoporosis in dominant model (OR=1.21, 95%CI 1.07-1.37, P=0.002). Significant in post-menopausal women subgroup (OR=1.29, P=0.005). Not significant when both genders pooled (P=0.12).",
        "relevance": "IGF1 rs35767 increases osteoporosis risk in post-menopausal women — the same SNP associated with athletic performance. With declining GH/IGF axis activity post-menopause, this SNP identifies candidates for bone-protective GH secretagogue interventions.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/29747606",
    },
    {
        "trait": TRAIT, "gene": "IGF1", "literature_type": "Systematic Review",
        "pmid": "28135889", "year": "2017",
        "title": "Association of IGF1 polymorphism rs6214 with high myopia: A systematic review and meta-analysis",
        "authors": "Zhang D, Zeng G, Hu J et al.",
        "journal": "Ophthalmic Genetics",
        "study_type": "Systematic Review + Meta-Analysis",
        "evidence": "Systematic Review",
        "snps": "IGF1 rs6214 (3'-UTR)",
        "design": "8 case-control studies; 4,242 myopia patients + 4,430 controls. PubMed, Embase, Web of Science, and Chinese Biomedical Database to June 2016. Fixed and random effects models. Begg's test for publication bias.",
        "findings": "No significant association between IGF1 rs6214 and high myopia in Chinese, Japanese, or pooled populations across any genetic model. Low heterogeneity across studies.",
        "relevance": "Null result for rs6214 x myopia establishes tissue-specificity of IGF1 SNP effects. rs6214's cancer-protective effect (per separate meta-analysis) does not extend to ocular refractive error — useful for understanding SNP pleiotropy.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/28135889",
    },
    {
        "trait": TRAIT, "gene": "IRS1", "literature_type": "Meta-Analysis",
        "pmid": "31248719", "year": "2019",
        "title": "Physical activity attenuates the association between the IRS1 genotype and childhood obesity in Chinese children",
        "authors": "Song Q, Song J, Li C et al.",
        "journal": "Nutr Metab Cardiovasc Dis",
        "study_type": "Meta-Analysis (4-cohort pooled study)",
        "evidence": "Meta-Analysis",
        "snps": "IRS1 rs2943650",
        "design": "IRS1 rs2943650 genotyped in 3,303 Chinese children (6-18 years) from 4 independent studies. Logistic/linear regression per study; meta-analysis to pool results. Gene x physical activity interaction tested.",
        "findings": "C-allele carriers: 29% higher obesity risk (OR=1.29, P=0.02) and +0.41 kg/m2 BMI. KEY INTERACTION: Inactive C-allele carriers had 241% increased obesity risk (OR=3.41, 95%CI 1.45-8.01, P=0.005) vs physically active counterparts. Physical activity fully attenuated the IRS1 risk allele obesity effect.",
        "relevance": "Landmark gene x lifestyle interaction meta-analysis for IRS1 in the GH/insulin axis. Physical activity completely eliminates the IRS1 rs2943650 obesity risk — the most actionable nutrigenetic finding in this collection.",
        "link": "https://pubmed.ncbi.nlm.nih.gov/31248719",
    },
]

# ─────────────────────────────────────────────────────────────────────────────
# MERGE & WRITE CSV
# ─────────────────────────────────────────────────────────────────────────────
all_papers = intervention_papers + meta_papers

HEADERS = [
    "Trait",
    "Gene",
    "Literature Type",
    "PMID",
    "Year",
    "Title",
    "Authors (First 3+)",
    "Journal",
    "Study Type",
    "Evidence Level",
    "Key SNP(s)",
    "Study Design / Methods",
    "Key Findings",
    "Nutrigenetic Relevance",
    "PubMed Link",
]

out_csv = "/home/daytona/workspace/gh-ghrelin-papers/GH_Ghrelin_Axis_Comprehensive.csv"
with open(out_csv, "w", newline="", encoding="utf-8") as f:
    writer = csv.DictWriter(f, fieldnames=HEADERS)
    writer.writeheader()
    for p in all_papers:
        writer.writerow({
            "Trait": p["trait"],
            "Gene": p["gene"],
            "Literature Type": p["literature_type"],
            "PMID": p["pmid"],
            "Year": p["year"],
            "Title": p["title"],
            "Authors (First 3+)": p["authors"],
            "Journal": p["journal"],
            "Study Type": p["study_type"],
            "Evidence Level": p["evidence"],
            "Key SNP(s)": p["snps"],
            "Study Design / Methods": p["design"],
            "Key Findings": p["findings"],
            "Nutrigenetic Relevance": p["relevance"],
            "PubMed Link": p["link"],
        })

print(f"Merged CSV saved: {out_csv}  ({len(all_papers)} total papers)")

cd /home/daytona/workspace/gh-ghrelin-papers && python3 build_merged.py

libreoffice --headless --convert-to xlsx --outdir /tmp/ /home/daytona/workspace/…

# Check file integrity and size ls -lh /home/daytona/workspace/gh-ghrelin-papers…

# Generate ODS format libreoffice --headless --convert-to ods --outdir /tmp/ /ho…

MET c-Met BDNF Val66Met polymorphism depression mood human study

SLC6A4 serotonin transporter 5-HTTLPR polymorphism depression intervention human

SLC6A1 GAT-1 GABA transporter polymorphism depression anxiety human

GABBR1 GABA-B receptor polymorphism SNP depression mood disorder human

GABBR2 GABA-B receptor 2 polymorphism SNP depression anxiety human study

SLC6A4 serotonin transporter polymorphism depression meta-analysis

BDNF Val66Met rs6265 depression antidepressant treatment response human

SLC6A1 polymorphism SNP psychiatric depression epilepsy humans

GABBR1 polymorphism depression anxiety bipolar human association study

GABBR2 polymorphism SNP mood disorder depression human

BDNF Val66Met depression meta-analysis antidepressant

PMID: 40772427

PMID: 35605794

PMID: 23733030

PMID: 40319044

PMID: 32991440

PMID: 32495670

PMID: 32219696

PMID: 24996193

SLC6A1 GAT1 GABA transporter SNP polymorphism depression anxiety psychiatric humans PubMed

GABBR1 GABBR2 GABA-B receptor SNP polymorphism depression anxiety bipolar disorder human study PubMed