Current Understanding of Genetic Architecture of Polyendocrine Metabolic Ovarian Syndrome (PMOS) - 2026 Update

Polyendocrine Metabolic Ovarian Syndrome (PMOS; formerly known as Polycystic Ovary Syndrome, PCOS) is a common, heterogeneous endocrinopathy of reproductive-age women with a frequency of 5-26% worldwide. PMOS is characterized by hyperandrogenemia, ovulatory dysfunction, and polycystic ovarian morphology. A systematic search of the NHGRI-EBI GWAS Catalog and the literature in PubMed identified 17 PMOS GWAS or GWAS Meta-analyses with loci with significant evidence for association with PMOS. The PMOS GWAS identified 120 genomic regions significantly associated with PMOS. Thirty-eight of the PMOS GWAS loci are detected in at least two cohorts, and the majority of replicated regions were observed in multiple ancestries. The genes encoded by PMOS GWAS loci are implicated in gonadotropin secretion and action, folliculogenesis, sex hormone function, age at menopause, adiposity, insulin signaling, T2DM, calcium signaling, endocytosis, lipid and cholesterol levels, and cardiometabolic disease.