Pediatric Features of Genetic Predisposition to Polycystic Ovary Syndrome.

Sep 11, 2023

Experts: Jia Zhu,Anders U Eliasen,Izzuddin M Aris,Sara E Stinson,Jens-Christian Holm,Torben Hansen,Marie-France Hivert,Klaus Bønnelykke,Rany M Salem,Joel N Hirschhorn,Yee-Ming Chan

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.
To identify childhood manifestations of genetic risk for PCOS.
We calculated a PCOS polygenic risk score (PRS) for 12,350 girls and boys in four 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.
Higher PRS for PCOS was associated with higher BMI in mid-childhood (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=0.0009); both persisted through late adolescence (p all ≤0.03). 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=0.005) 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).
Genetic risk factors for PCOS are associated with alterations in metabolic and growth and developmental traits in childhood. Thus, PCOS may not simply be a condition that affects reproductive-age women but, rather, one possible manifestation of an underlying condition that affects both sexes starting in early life.

© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.

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ABOUT THE EXPERTS

Jia Zhu,Anders U Eliasen,Izzuddin M Aris,Sara E Stinson,Jens-Christian Holm,Torben Hansen,Marie-France Hivert,Klaus Bønnelykke,Rany M Salem,Joel N Hirschhorn,Yee-Ming Chan

Jia Zhu

Division of Endocrinology, Boston Children’s Hospital, Boston, MA, USA.

Programs in Metabolism and Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Anders U Eliasen

Copenhagen Prospective Studies on Asthma in Childhood Research Center (COPSAC), Copenhagen, Denmark.

Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, Kongens Lyngby, Denmark.

Izzuddin M Aris

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School, Harvard University and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Sara E Stinson

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Jens-Christian Holm

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

The Children’s Obesity Clinic, accredited European Centre for Obesity Management, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark.

Torben Hansen

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Marie-France Hivert

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School, Harvard University and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.

Klaus Bønnelykke

Copenhagen Prospective Studies on Asthma in Childhood Research Center (COPSAC), Copenhagen, Denmark.

Rany M Salem

Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.

Joel N Hirschhorn

Division of Endocrinology, Boston Children’s Hospital, Boston, MA, USA.

Programs in Metabolism and Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Department of Genetics, Harvard Medical School, Boston, MA, USA.

Yee-Ming Chan

Division of Endocrinology, Boston Children’s Hospital, Boston, MA, USA.

Programs in Metabolism and Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Department of Pediatrics, Harvard Medical School, Boston, MA, USA.