Abstract

Polycystic ovary syndrome (PCOS) is among the most common disorders of reproductive-age women, affecting up to 15% worldwide, depending on the diagnostic criteria. PCOS is characterized by a constellation of interrelated reproductive abnormalities including disordered gonadotropin secretion, increased androgen production, chronic anovulation, and polycystic ovarian morphology. It is frequently associated with insulin resistance and obesity. These reproductive and metabolic derangements cause major morbidities across the lifespan, including anovulatory infertility and type 2 diabetes (T2D).Despite decades of investigative effort, the etiology of PCOS remains unknown. Familial clustering of PCOS cases has indicated a genetic contribution to PCOS. There are rare Mendelian forms of PCOS associated with extreme phenotypes, but PCOS typically follows a non-Mendelian pattern of inheritance consistent with a complex genetic architecture, analogous to T2D and obesity, that reflects the interaction of susceptibility genes and environmental factors. Genomic studies of PCOS have provided important insights into disease pathways and have indicated that current diagnostic criteria do not capture underlying differences in biology associated with different forms of PCOS.We provide a state-of-the-science review of genetic analyses of PCOS, including an overview of genomic methodologies aimed at a general audience of non-geneticists and clinicians. Applications in PCOS will be discussed, including strengths and limitations of each study. The contributions of environmental factors, including developmental origins, will be reviewed. Insights into the pathogenesis and genetic architecture of PCOS will be summarized. Future directions for PCOS genetic studies will be outlined.

中文翻译：

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解构综合征：对 PCOS 因果机制和分类的基因组洞察

摘要

多囊卵巢综合征 (PCOS) 是育龄妇女最常见的疾病之一，根据诊断标准，全球患病率高达 15%。PCOS 的特征是一系列相互关联的生殖异常，包括促性腺激素分泌紊乱、雄激素产生增加、慢性无排卵和多囊卵巢形态。它通常与胰岛素抵抗和肥胖有关。这些生殖和代谢紊乱导致整个生命周期的主要发病率，包括无排卵性不孕症和 2 型糖尿病 (T2D)。尽管经过数十年的调查努力，PCOS 的病因仍然未知。PCOS 病例的家族聚集表明遗传对 PCOS 的贡献。有罕见的孟德尔形式的 PCOS 与极端表型相关，但 PCOS 通常遵循与复杂遗传结构一致的非孟德尔遗传模式，类似于 T2D 和肥胖症，这反映了易感基因和环境因素的相互作用。PCOS 的基因组研究提供了对疾病途径的重要见解，并表明当前的诊断标准没有捕捉到与不同形式的 PCOS 相关的生物学潜在差异。我们提供了 PCOS 遗传分析的最新科学回顾，包括针对非遗传学家和临床医生的一般受众的基因组方法概述。将讨论在 PCOS 中的应用，包括每项研究的优势和局限性。将审查环境因素的贡献，包括发展起源。将总结对 PCOS 发病机制和遗传结构的见解。将概述 PCOS 遗传研究的未来方向。