Endometriosis & Uterine Health

Intergenic GWAS locus near EIF4EBP1 (encoding the mTOR translation repressor 4E-BP1) where the T allele is associated with modestly lower circulating anti-Müllerian hormone (AMH), a key biomarker of ovarian reserve and fertility timing

A regulatory tag SNP in the IL1A/IL1B locus on chromosome 2q13; the G allele increases endometriosis risk (OR 1.12) and correlates with elevated IL-1 alpha expression, driving peritoneal inflammation and ectopic lesion establishment.

3'UTR variant that controls GDF15 expression via microRNA regulation — C allele raises baseline GDF15 (metabolic and atherosclerosis risk); G allele lowers it (increased pregnancy nausea sensitivity)

Intronic variant near the VEZT (vezatin) gene at 12q22 associated with increased endometriosis susceptibility across multiple GWAS meta-analyses; the C allele acts as a cis-eQTL increasing VEZT expression in blood and endometrial tissue, implicating disrupted adherens junction integrity in ectopic endometrial implantation

Intronic GREB1 variant at 2p25.1 where the T allele (GRCh38 reference) is associated with increased endometriosis risk; the G allele confers protection. Identified independently of the nearby rs13394619 GREB1 variant (r²=0.65 in Europeans — moderate LD, not redundant), with OR=1.13 and P=3×10⁻¹⁷ for all endometriosis and OR=1.16 (P=6×10⁻⁹) for stage 3/4 disease in the 2023 Rahmioglu Nature Genetics GWAS.

Intronic variant in the fibronectin 1 gene associated with increased susceptibility to endometriosis, particularly moderate-to-severe disease; the A allele may influence transcription factor binding and FN1 expression, altering extracellular matrix remodeling in ectopic endometrial implants

X-linked intronic variant in IL1RAPL2, a synaptic adhesion gene expressed exclusively in the central nervous system; carried as a haplotype associated with thyrotoxic hypokalaemic periodic paralysis in a Thai cohort, though this association was not replicated in a Korean population

Intergenic GWAS locus upstream of homeobox genes HOXA10 and HOXA11 that may influence their regulation; carrying the A allele is associated with increased risk of endometriosis, particularly moderate-to-severe disease

Intronic variant in the immune-response gene EPSTI1, associated in recessive models with reduced sperm concentration, total sperm count, sperm motility, and azoospermia/oligospermia risk in men.

Regulatory variant near the NPR3 natriuretic peptide clearance receptor gene associated with gestational hypertension and preeclampsia risk; the C allele may increase NPR3-mediated peptide clearance, impairing vasodilatory natriuretic signaling during pregnancy

PCOS-susceptibility tag SNP at the IRF1/RAD50 5q31 locus, associated with elevated testosterone levels and modestly increased PCOS risk in women of European ancestry

Intronic variant in GREB1, an estrogen-responsive gene; the G allele is associated with increased risk of endometriosis, particularly moderate-to-severe disease, across European and East Asian populations

An intronic insertion/deletion variant in the neuropeptide S receptor 1 gene associated with stage III/IV endometriosis; the deletion allele tags regulatory variation that amplifies NPSR1-driven neuroinflammatory signalling in the peritoneal environment, implicating a nonhormonal pain and inflammation pathway in advanced disease.

Intronic GREB1 variant at 2p25.1 (c.772+34) in high LD (r²=0.853 CEU) with the established endometriosis lead SNP rs11674184; the T allele tags the rs11674184-T endometriosis susceptibility signal and is the risk-associated allele at this locus

Regulatory variant in the ANRIL long non-coding RNA at the 9p21.3 locus; the C allele independently increases endometriosis susceptibility, with stronger effects in moderate-to-severe disease stages

Intergenic variant ~17 kb upstream of KDR (encoding VEGFR2, the primary VEGF receptor) on chromosome 4q12; the G allele is associated with increased endometriosis risk and is the lead tagging variant for a locus where disease susceptibility tracks with severity of neovascularization in ectopic lesions

Intronic variant in CCDC170 at the 6q25.1 estrogen-signaling locus, co-regulated with ESR1; the C allele increases endometriosis risk (OR 1.09) and has been independently replicated across European, East Asian, and Taiwanese-Han populations

Promoter-region variant upstream of estrogen receptor alpha (ESR1) at 6q25.1; the A allele increases ESR1 transcription and is associated with elevated endometriosis risk, endometrial cancer susceptibility, and breast cancer risk across multiple populations

Intronic variant in the estrogen receptor alpha gene at the 6q25.1 locus independently associated with endometriosis susceptibility; the T allele modestly increases risk (OR ~1.10) and lies near ARMT1 (Acidic Residue Methyltransferase 1), influencing estrogen-sensitive gene regulation at this replicated endometriosis GWAS locus

Intronic variant near ZNF346 and FGFR4 on chromosome 5q35.2, associated with uterine fibroid (leiomyoma) risk via cis-eQTL upregulation of FGFR4 and UIMC1

3' UTR variant in IL1A (interleukin-1 alpha) associated with endometriosis susceptibility across multiple ethnic populations; one of eight replicated IL1A locus SNPs linked to the chronic pelvic inflammatory environment that promotes ectopic endometrial implantation.

Intronic variant in the HLA class II region associated with nonobstructive azoospermia risk, likely through immune-mediated disruption of testicular spermatogenesis

Intronic variant within IL1A (Interleukin-1 alpha) associated with endometriosis risk in Japanese and European GWAS; the G allele increases susceptibility by tagging IL-1α-driven peritoneal inflammation at a locus replicated across ancestries

Intronic variant in WNT4 on chromosome 1p36.12 that introduces a high-affinity estrogen receptor alpha binding site, upregulating WNT4 in endometrial stromal cells; the T allele is associated with increased endometriosis and uterine fibroid risk through enhanced stromal invasibility, while the C allele associates with pelvic organ prolapse risk — an example of antagonistic pleiotropy in reproductive tissue biology

Intronic variant in VEZT (vezatin, adherens junction transmembrane protein) on chromosome 12q23.2; the T allele is associated with increased endometriosis risk across multiple large GWAS meta-analyses, with an odds ratio of approximately 1.08 per allele

Intronic variant in TMEM150B (19q13.42) associated with age at natural menopause and early menopause risk; the C allele may contribute to earlier follicular depletion, while the T allele has been linked to higher oocyte yield during controlled ovarian stimulation.

IL1B promoter -3737 G/A variant that modulates interleukin-1β expression; the A allele is associated with reduced IL-1β promoter activity, potentially lowering the chronic peritoneal inflammatory load implicated in endometriosis pathogenesis

Intronic variant in TSBP1-AS1 (LOC101929163), a non-coding antisense RNA in the HLA region between TSBP1 and BTNL2 on chromosome 6p21.32; the G allele is associated with increased risk of non-obstructive azoospermia in Han Chinese men, with an odds ratio of approximately 1.42 in a large multi-stage GWAS

Intronic variant in TTC39B (9p22) that increases endometriosis susceptibility; the T allele carries an OR of 1.29 for endometriosis, with a stronger effect on stage III/IV disease (OR 1.35). TTC39B is a regulator of LXR protein stability that controls HDL cholesterol metabolism, suggesting the endometriosis association may act through lipid-mediated inflammatory signalling in the peritoneal environment.

Intronic variant in SIRT3 (the principal mitochondrial deacetylase) associated with uterine fibroid risk; the common T allele is linked to modestly higher fibroid susceptibility while the rarer C allele appears protective, likely through effects on SIRT3 expression and mitochondrial oxidative-stress defence in uterine smooth muscle

Regulatory variant near the IL1A (Interleukin-1 alpha) gene associated with moderate-to-severe endometriosis risk; the C allele increases risk (OR 1.21) by modulating IL-1α-driven peritoneal inflammation, adhesion formation, and ectopic endometrial tissue implantation

Intergenic 6q25.1 variant between CCDC170 and ESR1; the C allele is an eQTL for CCDC170 expression and is associated with breast cancer risk, bone density, and estrogen-sensitive tissue proliferation

Rare intronic variant in EIF2AK3-AS1, an antisense long non-coding RNA that regulates expression of EIF2AK3 (PERK), the kinase mediating the endoplasmic reticulum unfolded protein response; PERK pathway activation is documented in endometriotic tissue, linking ER stress to ectopic lesion survival and ovarian damage in endometriosis

An intronic variant in SYNE1 (Nesprin-1) at the 6q25.1 locus, first identified as a genome-wide significant endometriosis locus in the 2017 Sapkota meta-analysis and confirmed in the 2023 Rahmioglu mega-GWAS; the G allele is associated with endometriosis risk overall (OR ~1.11) and strongly enriched for pain subphenotypes including dysmenorrhea (OR ~1.49) and dyspareunia (OR ~2.07), implicating a neuromechanical rather than purely hormonal pathway

Intronic TERT variant that increases uterine fibroid (leiomyoma) risk through impaired telomere maintenance and genome stability, independent of the longevity TERT variants

An intronic regulatory variant in ESR1 at the 6q25.1 locus identified as a high-confidence causal endometriosis SNP (posterior inclusion probability 0.506) through fine-mapping of the Rahmioglu et al. 2023 mega-GWAS; the T allele lies in strong LD with eQTLs driving ESR1 expression and DNA methylation near ESR1, implicating altered estrogen receptor signaling in endometriosis susceptibility and pain subphenotypes including dysmenorrhea and dyspareunia

Intronic variant near WNT4 on chromosome 1p36.12 associated in multiple GWAS with elevated risk of endometriosis, particularly moderate-to-severe (stage III/IV) disease, and with uterine fibroid susceptibility through disrupted Wnt signaling in the endometrium.

Intergenic variant near STN1 (telomere maintenance) and SLK (cytoskeletal kinase) associated with uterine fibroid risk in multiple GWAS

Intronic variant in FOXO1, a pro-apoptotic transcription factor whose suppression by the AKT/progestin pathway promotes uterine fibroid cell survival; the G allele is associated with elevated uterine leiomyoma risk in multiple GWAS, while the A allele associates with later age at natural menopause.

Intronic variant in PLCE1 (phospholipase C epsilon 1) associated with elevated systolic and diastolic blood pressure; the G allele has been linked in large GWAS to modestly higher blood pressure and, through shared genetic architecture, to increased susceptibility to preeclampsia and other hypertensive disorders of pregnancy

3' UTR variant in CCDC170 at the 6q25.1 estrogen-signaling locus; the T allele disrupts a miR-27a binding site, reducing CCDC170 expression and increasing breast cancer risk (OR 1.38 in Chinese women); the same locus independently confers endometriosis susceptibility