Fertility & Reproductive Health

Intronic variant in the androgen-regulating DENND1A gene associated with polycystic ovary syndrome (PCOS) risk; the G allele is linked to increased PCOS susceptibility and elevated post-load insulin levels, primarily in East Asian and Han Chinese populations

Intronic variant in the LH/choriogonadotropin receptor gene associated with PCOS susceptibility and elevated androgen levels, predominantly in Asian and East African populations

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

Promoter variant reducing FSH beta-subunit transcription by ~50%, lowering serum FSH levels and impairing folliculogenesis in females and spermatogenesis in males

Distal enhancer variant ~26 kb upstream of FSHB associated with FSH levels, dizygotic twinning, PCOS susceptibility, age at menopause, and male reproductive parameters

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

Missense variant in the MCM8 DNA repair helicase associated with ovarian reserve and age at natural menopause; the A allele is linked to higher AMH levels and later menopause onset.

Missense variant in PRRC2A (HLA-B associated transcript) linked to age at natural menopause through immune-mediated oocyte depletion; the A allele may be associated with earlier menopause onset

Intronic variant in FNDC4 (fibronectin type III domain containing 4) on chromosome 2; the T allele is associated with earlier age at natural menopause and increased risk of primary ovarian insufficiency through disruption of follicular granulosa cell signaling.

Regulatory variant near LIN28B associated with puberty timing — the T allele is linked to earlier menarche in females and earlier puberty in males, with implications for reproductive window length and age-at-onset of fertility

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.

Missense variant in the extracellular domain of the FSH receptor that removes an O-linked glycosylation site, altering FSH binding affinity; nearly completely co-inherited with rs6166 (Asn680Ser) and associated with poor ovarian response in IVF and PCOS susceptibility

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

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.

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

Intronic variant in LIN28B associated with puberty timing — the C allele may be linked to earlier menarche in females and earlier puberty milestones in males, with implications for reproductive window length and cumulative estrogen exposure

Intronic variant in ZNF346 (chromosome 5q35.2), a proxy SNP for the UIMC1/RAP80 DNA-repair locus; the G allele may be associated with earlier age at natural menopause and modestly increased susceptibility to primary ovarian insufficiency

Intronic variant in TLK1 (tousled like kinase 1), a DNA-damage-repair and chromatin-assembly kinase; each copy of the T allele may be associated with earlier age at natural menopause by approximately 10 weeks, suggesting a modest influence on ovarian reserve and reproductive lifespan

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

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

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

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 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.

Coding variant in aromatase that substitutes cysteine for arginine at position 264; in vitro evidence shows increased aromatase activity, with reported associations with PCOS risk and ART pregnancy outcomes in some populations

Intronic variant in HSPA4L within a chromosome 4 haplotype spanning PLK4; the A allele is associated with increased mitotic-origin embryo aneuploidy, reduced blastocyst formation in IVF, and elevated early recurrent miscarriage risk in women; HSPA4L itself is highly expressed in spermatogenic cells and required for normal sperm production

Affects LH/hCG receptor sensitivity near a glycosylation site, influencing ovarian response to LH stimulation, PCOS risk, ovarian aging, and IVF outcomes