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Family-based and extensive genome-wide association studies have yielded 17 replicated PCOS risk genes, regulating gonadotropin secretion (FSHB), gonadotropin action and ovarian function (LHCGR, FSHR, DENND1A, RAB5/SUOX, HMGA2, C9orf3, YAP1, TOX3, RAD50, FBN3), and various metabolic functions (THADA, GATA4/NEIL2, ERBB4, SUMO1P1, INSR,and KRR1) [46–48]. Of the genes regulating gonadotropin and ovarian function, a substantial number have been proposed as enabling ovarian hyperandrogenism [46, 49]. A recent alternative approach, employing rare gene variant association testing, followed by targeted resequencing of AMH in a replication cohort, identified an additional 17 PCOS-specific, rare coding and splice-site variants in AMH that diminish AMH signaling [49]. Ovarian hyperandrogenism is a potential outcome of reduced ovarian AMH inhibition of CYP17A1 expression [49]. While progress toward understanding gene variant-based PCOS heritability has clearly advanced, a heritability gap between low incidence of PCOS risk genes (∼10%) and the high heritability of PCOS (∼70%) [50], indicates a pressing need to identify (1) more PCOS risk genes, as each may confer a small degree of disease risk, (2) rare gene variants, as each may confer unduly large degrees of PCOS risk, and/or (3) epigenetic mechanisms altering a wide range of gene expression that confer considerable risk for PCOS. Current thinking embraces a combination of polygenic, epigenetic, and developmental contributions to PCOS pathogenesis that are ameliorated or exaggerated by lifestyle [1, 47].