Pediatric Features of Genetic Predisposition to Polycystic Ovary Syndrome
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Pediatric Features of Genetic Predisposition to Polycystic Ovary Syndrome. / Zhu, Jia; Eliasen, Anders U; Aris, Izzuddin M; Stinson, Sara E; Holm, Jens-Christian; Hansen, Torben; Hivert, Marie-France; Bønnelykke, Klaus; Salem, Rany M; Hirschhorn, Joel N; Chan, Yee-Ming.
I: Journal of Clinical Endocrinology and Metabolism, Bind 109, Nr. 2, 2024, s. 380-388.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Pediatric Features of Genetic Predisposition to Polycystic Ovary Syndrome
AU - Zhu, Jia
AU - Eliasen, Anders U
AU - Aris, Izzuddin M
AU - Stinson, Sara E
AU - Holm, Jens-Christian
AU - Hansen, Torben
AU - Hivert, Marie-France
AU - Bønnelykke, Klaus
AU - Salem, Rany M
AU - Hirschhorn, Joel N
AU - Chan, Yee-Ming
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2024
Y1 - 2024
N2 - 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 fixedeffect 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.
AB - 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 fixedeffect 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.
U2 - 10.1210/clinem/dgad533
DO - 10.1210/clinem/dgad533
M3 - Journal article
C2 - 37690116
VL - 109
SP - 380
EP - 388
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 2
ER -
ID: 368207892