@article{8715b0488a2d40babceec9a4eb219d7f,
title = "Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome",
abstract = "Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic study (n = 544,513), we expand the number of genetic loci from 16 to 29, and additionally identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to an increased oocyte number and/or availability across the lifespan. Hormonal regulation in the etiology of this condition, through metabolic and reproductive features, was emphasized. The proteomic analysis highlighted metabolic biology known to be related to PCOS. A polygenic risk score (PRS) was associated with adverse cardiometabolic outcomes, with differing relevance of testosterone and body mass index in women and men. Finally, while oligo-anovulation and anovulatory infertility are features of PCOS, we observed no impact of PCOS susceptibility on childlessness. We suggest that PCOS susceptibility confers balanced pleiotropic influences on fertility in women, and life-long adverse metabolic consequences in both sexes.",
keywords = "Impaired glucose-tolerance, Reported oligo-amenorrhea, Anti-mullerian hormone, Mendelian randomization, Wide association, Follow-up, Genetic-variants, Fsh-levels, Women, Risk, Body Mass Index, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Middle Aged, Male, Genomics/methods, Multifactorial Inheritance, Polycystic Ovary Syndrome/genetics, Proteomics, Female, Adult, Polymorphism, Single Nucleotide, Testosterone/blood",
author = "Moolhuijsen, \{Loes M E\} and Jia Zhu and Mullin, \{Benjamin H\} and Nat{\`a}lia Pujol-Gualdo and Actkins, \{Ky'Era V\} and Mack, \{Jasmine A\} and Hridya Rao and Bhavi Trivedi and Kentistou, \{Katherine A\} and Yajie Zhao and David Westergaard and Tyrmi, \{Jaakko S\} and Gudmar Thorleifsson and Yanfei Zhang and Laura Wittemans and Amber DeVries and Kelly Brewer and Ryan Sisk and Rebecca Danning and Preuss, \{Michael H\} and Jones, \{Michelle R\} and Ruth, \{Katherine S\} and Marianne Andersen and Ricardo Azziz and Karina Banasik and Michael Boehnke and Linda Broer and S{\o}ren Brunak and Yee-Ming Chan and Chasman, \{Daniel I\} and Mark Daly and Ehrmann, \{David A\} and Fauser, \{Bart C\} and Fritsche, \{Lars G\} and Hayes, \{M Geoffrey\} and Chunyan He and Hongyan Huang and Irina Kowalska and Peter Kraft and Legro, \{Richard S\} and Nan Lin and Loos, \{Ruth J\} and Louwers, \{Yvonne V\} and Reedik Magi and McCarthy, \{Mark I\} and Laure Morin-Papunen and Morrison, \{Jean V\} and Cynthia Morton and Nadkarni, \{Girish N\} and Pedersen, \{Ole B V\} and Day, \{Felix R\} and \{Genes and Health Research Team\}",
note = "{\textcopyright} 2026. The Author(s).",
year = "2026",
month = may,
doi = "10.1038/s41588-026-02543-9",
language = "English",
volume = "58",
pages = "1040--1050",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "5",
}