Suppr超能文献

大规模全基因组荟萃分析多囊卵巢综合征表明不同诊断标准具有共同的遗传结构。

Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.

机构信息

MRC Epidemiology Unit, Cambridge Biomedical Campus, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.

The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

出版信息

PLoS Genet. 2018 Dec 19;14(12):e1007813. doi: 10.1371/journal.pgen.1007813. eCollection 2018 Dec.

Abstract

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health.

摘要

多囊卵巢综合征(PCOS)是一种以高雄激素血症、排卵功能障碍和多囊卵巢形态为特征的疾病。受影响的女性常伴有代谢紊乱,包括胰岛素抵抗和葡萄糖稳态失调。PCOS 有两套不同的诊断标准,导致 PCOS 病例表现出不同的表型谱。基于这两个标准诊断的病例之间的遗传相似性在很大程度上是未知的。以前在中国和欧洲人群中的研究已经确定了 16 个与 PCOS 风险相关的基因座。我们报告了一项基于欧洲血统的 10074 例 PCOS 病例和 103164 例对照的固定效应、逆加权方差荟萃分析,以及 PCOS 相关特征的描述。我们确定了 3 个新的基因座(靠近 PLGRKT、ZBTB16 和 MAPRE1),并对 11 个先前报道的基因座进行了复制。只有一个基因座在其与诊断标准的相关性上存在显著差异;否则,通过自我报告和 NIH 或非 NIH 鹿特丹标准诊断的 PCOS 在 13 个基因座的常见变异体中具有相似的遗传结构。鉴定出的变异体与受影响女性的高雄激素血症、促性腺激素调节和睾酮水平相关。连锁不平衡评分回归分析显示,与肥胖、空腹胰岛素、2 型糖尿病、血脂水平和冠心病存在遗传相关性,表明代谢特征与 PCOS 之间存在共同的遗传结构。孟德尔随机化分析表明,与体重指数、空腹胰岛素、绝经时间、抑郁和男性型秃发相关的变异体在 PCOS 中起因果作用。因此,这些数据表明 3 个新的基因座与 PCOS 相关,所有诊断标准的遗传结构相似。这些数据还首次为 PCOS 的男性表型提供了遗传证据,并为之前假设的合并疾病抑郁提供了因果关系。因此,遗传学为 PCOS 提供了一个全面的视角,包括多种诊断标准、性别、生殖潜力和心理健康。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c0/6300389/159825bfe0cd/pgen.1007813.g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验