Polycystic Ovary Syndrome Susceptibility Loci Inform Disease Etiological Heterogeneity

Polycystic ovary syndrome (PCOS) is a complex disorder with heterogenous phenotypes and unclear etiology. A recent phenotypic clustering study identified metabolic reproductive subtypes of PCOS. We hypothesize that the heterogeneity PCOS manifestations reflects different mechanistic pathways can be using genetic approach. applied k-means to categorize genome-wide significant variants into clusters based on their associations selected quantitative traits likely reflect etiological pathways. evaluated association each cluster PCOS-related disease outcomes. then Mendelian randomization estimate causal effects between Three categories were identified: adiposity, insulin resistant, reproductive. Significant observed for in adiposity body mass index (BMI), waist circumference breast cancer, insulin-resistant fasting insulin, glucose values, homeostatic model assessment resistance (HOMA-IR). Sex hormone binding globulin (SHBG) has strong all three clusters. suggested role BMI SHBG No