Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, China.
Nat Genet. 2012 Sep;44(9):1020-5. doi: 10.1038/ng.2384. Epub 2012 Aug 12.
Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.
在包含 744 例病例和 895 例对照的全基因组关联研究(GWAS1)之后,我们分析了一个新的汉族人群(GWAS2)的全基因组关联数据,其中包括 1510 例多囊卵巢综合征(PCOS)病例和 2016 例对照。我们在总共 8226 例病例和 7578 例对照的 GWAS1 和 2 的合并结果中对显著相关的信号进行了随访。除了确认我们之前报道的三个位点外,我们还在 P < 5 × 10(-8)的水平上确定了 8 个新的 PCOS 关联信号:9q22.32、11q22.1、12q13.2、12q14.3、16q12.1、19p13.3、20q13.2 和第二个独立信号位于 2p16.3(FSHR 基因)。这些 PCOS 关联信号表明候选基因与胰岛素信号、性荷尔蒙功能和 2 型糖尿病(T2D)有关,具有富集的证据。其他候选基因与钙信号和内吞作用有关。我们的研究结果为发现 PCOS 的生物学机制提供了新的见解和方向。