Year: 2023
Type: article
Study design: Observational Study
Abstract: CONTEXT: Polycystic ovary syndrome (PCOS) has historically been conceptualized as a disorder of the reproductive system in women. However, offspring of women with PCOS begin to show metabolic features of PCOS in childhood, suggestive of childhood manifestations. OBJECTIVE: To identify childhood manifestations of genetic risk for PCOS. METHODS: We calculated a PCOS polygenic risk score (PRS) for 12 350 girls and boys in 4 pediatric cohorts-ALSPAC (UK), COPSAC (Denmark), Project Viva (USA), and The HOLBÆK Study (Denmark). We tested for association of the PRS with PCOS-related phenotypes throughout childhood and with age at pubarche and age at peak height velocity and meta-analyzed effects across cohorts using fixed-effect models. RESULTS: Higher PRS for PCOS was associated with higher body mass index in midchildhood (0.05 kg/m2 increase per 1 SD of PRS, 95% CI 0.03, 0.07, P = 3 × 10-5) and higher risk of obesity in early childhood (OR 1.34, 95% CI 1.13, 1.59, P = .0009); both persisted through late adolescence (P all ≤.03). Higher PCOS PRS was associated with earlier age at pubarche (0.85-month decrease per 1 SD of PRS, 95% CI -1.44, -0.26, P = .005) and younger age at peak height velocity (0.64-month decrease per 1 SD of PRS, 95% CI -0.94, -0.33, P = 4 × 10-5). CONCLUSION: Genetic risk factors for PCOS are associated with alterations in metabolic, growth, and developmental traits in childhood. Thus, PCOS may not simply be a condition that affects women of reproductive age but, rather, a possible manifestation of an underlying condition that affects both sexes starting in early life.
Institutions: Broad Institute, Boston Children's Hospital, Harvard University, Massachusetts Institute of Technology, Copenhagen University Hospital, Gentofte Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Technical University of Denmark, Harvard Pilgrim Health Care, University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, Holbæk Sygehus, Massachusetts General Hospital, University of California San Diego
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,400
Funders: American Heart Association, Wellcome Trust, Innovationsfonden, Pediatric Endocrine Society, University of Bristol, Novo Nordisk, Novo Nordisk Fonden, National Institutes of Health, Medical Research Council, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1180559200, G1224050641, G3150562068, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G3914068983, G479118285, Dissecting PCOS Physiology by Defining Phenotypes Associated with PCOS Genetic Risk Factors in Men and Children, Investigation of the influence of habitual level of vigorous physical activity on skeletal strength in late adolescence., G6689231961, G6983975130, Maternal overnutrition and offspring fat mass, metabolic and vascular function., G801210579, G8393905554, Common and distinct early environmental influences on cardiometabolic and respiratory health: Mechanisms and methods, G9000154342, Biological Insights from Genetic Investigation of ANthropometric Traits (GIANT) Across the Allelic Spectrum
OpenAlex ID: W4386586997