Current understanding of the genetic architecture of polyendocrine metabolic ovarian syndrome-2026 update

Polyendocrine metabolic ovarian syndrome (PMOS); formerly known as polycystic ovary syndrome) is a common, heterogeneous endocrinopathy of reproductive-age women with a frequency of 5%-26% worldwide. Polyendocrine metabolic ovarian syndrome is characterized by hyperandrogenemia, ovulatory dysfunction, and polycystic ovarian morphology. A systematic search of the National Human Genome Research Institute-European Bioinformatics Institute genome-wide association studies (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 were detected in at least two cohorts, and most replicated regions were observed across 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, type 2 diabetes mellitus, calcium signaling, endocytosis, lipid and cholesterol levels, and cardiometabolic disease.