Pediatric Features of Genetic Predisposition to Polycystic Ovary Syndrome

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

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

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.

OriginalsprogEngelsk
Sider (fra-til)380-388
Antal sider9
TidsskriftThe Journal of clinical endocrinology and metabolism
Vol/bind109
Udgave nummer2
Tidlig onlinedato10 sep. 2023
DOI
StatusUdgivet - 18 jan. 2024

Bibliografisk note

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

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