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Get Free AccessPolycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic and proteomic study, we expand the number of genetic loci from 19 to 29, and identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to a larger functional ovarian reserve. Hormonal regulation in the aetiology of this condition, through metabolic and reproductive features, was emphasised. The proteomic analysis highlighted perturbations of metabolically-related biology that are typical in women with PCOS. A PCOS polygenic risk score was associated with adverse cardio-metabolic outcomes, with differing contributions of testosterone and BMI in women and men. Finally, while oligo- and anovulatory infertility are characteristic 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.
Loes M E Moolhuijsen, Jia Zhu, Benjamin H. Mullin, Natàlia Pujol‐Gualdo, Ky’Era V. Actkins, Jasmine A. Mack, Hridya Rao, Bhavi Trivedi, Katherine A. Kentistou, Yajie Zhao, David Westergard, Jaakko Tyrmi, Guðmar Þorleifsson, Yanfei Zhang, Laura B. L. Wittemans, Amber A DeVries, Kelly Brewer, Ryan Sisk, Rebecca Danning, Michael Preuß, Michelle R. Jones, Katherine S. Ruth, Marianne Andersen, Ricardo Azziz, Karina Banasik, Michael Boehnke, Linda Broer, Søren Brunak, Yee-Ming Chan, Daniel I. Chasman, Mark J. Daly, David A. Ehrmann, Bart C.J.M. Fauser, Lars G. Fritsche, M. Geoffrey Hayes, Chunyan He, Hongyan Huang, Irina Kowalska, Peter Kraft, Richard S. Legro, Nan Lin, Ruth J. F. Loos, Yvonne V. Louwers, Reedik Mägi, Mark I. McCarthy, Laure Morin‐Papunen, Jean Morrison, Cynthia C. Morton, Girish N. Nadkarni, Benjamin M. Neale, Henriette Svarre Nielsen, Mette Nyegaard, Sisse Rye Ostrowski, Ole Birger Pedersen, Erik Sørensen, Christina Mikkelsen, Christian Erikstrup, Kathrine Agergård Kaspersen, Mie Topholm Bruun, Bitten Aagaard, Henrik Ullum, Barbara Obermayer‐Pietsch, Ken K. Ong, Aarno Palotie, Mary Pat Reeve, Andres Salumets, Richa Saxena, Timothy D. Spector, Bronwyn Stuckey, Unnur Þorsteinsdóttir, André G. Uitterlinden, Margrit Urbanek, Sebastian Zöllner, David A. van Heel, Joel N. Hirschhorn, Hreinn Stefánsson, John R. B. Perry, Unnur Styrkársdóttir, Scott G. Wilson, Terhi Piltonen, Triin Laisk, Paul M Ridker, Kharis Burns, Anne E. Justice, Hannele Laivuori, Mark O. Goodarzi, Lea K. Davis, Andrea Dunaif, Cecilia M. Lindgren, Joop S.E. Laven, Stephen Franks, Jenny A. Visser, Corrine K. Welt, Tugce Karaderi, Felix R. Day (2024). Genomic and proteomic evidence for hormonal and metabolic foundations of polycystic ovary syndrome. , DOI: https://doi.org/10.1101/2024.04.18.24306020.
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Type
Preprint
Year
2024
Authors
95
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1101/2024.04.18.24306020
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