Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.
Programs in Metabolism and Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
J Clin Endocrinol Metab. 2024 Jan 18;109(2):380-388. doi: 10.1210/clinem/dgad533.
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 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.
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).
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.
多囊卵巢综合征（PCOS）在历史上被认为是女性生殖系统的一种疾病。然而，患有 PCOS 的女性的后代在儿童期就开始表现出 PCOS 的代谢特征，这表明存在儿童期表现。
确定 PCOS 的遗传风险的儿童期表现。
我们为 4 个儿科队列（英国的 ALSPAC、丹麦的 COPSAC、美国的 Project Viva 和丹麦的 The HOLBÆK 研究）中的 12350 名女孩和男孩计算了 PCOS 多基因风险评分（PRS）。我们测试了 PRS 与整个儿童期 PCOS 相关表型以及青春期启动年龄和峰值身高速度年龄的相关性，并使用固定效应模型对队列进行荟萃分析。
较高的 PCOS PRS 与儿童中期的体重指数增加相关（PRS 每增加 1 个标准差，体重指数增加 0.05kg/m2，95%CI 0.03，0.07，P = 3×10-5），与儿童早期肥胖的风险增加相关（OR 1.34，95%CI 1.13，1.59，P =.0009）；两者在青春期后期都持续存在（P 均≤.03）。较高的 PCOS PRS 与青春期启动年龄提前相关（PRS 每增加 1 个标准差，青春期启动年龄提前 0.85 个月，95%CI -1.44，-0.26，P =.005），与峰值身高速度年龄较小相关（PRS 每增加 1 个标准差，峰值身高速度年龄提前 0.64 个月，95%CI -0.94，-0.33，P = 4×10-5）。
PCOS 的遗传风险因素与儿童期代谢、生长和发育特征的改变有关。因此，PCOS 可能不仅仅是一种影响育龄妇女的疾病，而是一种可能影响两性从生命早期开始的潜在疾病的表现。
