Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.
Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.
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DOI：
10.1038/ncomms8502
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发表时间：
2015-08-18
影响因子：
16.6
通讯作者：
Dunaif A
中科院分区：
文献类型：
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作者：
Hayes MG;Urbanek M;Ehrmann DA;Armstrong LL;Lee JY;Sisk R;Karaderi T;Barber TM;McCarthy MI;Franks S;Lindgren CM;Welt CK;Diamanti-Kandarakis E;Panidis D;Goodarzi MO;Azziz R;Zhang Y;James RG;Olivier M;Kissebah AH;Reproductive Medicine Network;Stener-Victorin E;Legro RS;Dunaif A
多囊卵巢综合征（PCOS）是一种常见的、病因不明的高度遗传性复杂疾病，以高雄激素血症、慢性无排卵和葡萄糖稳态缺陷为特征。促黄体生成素相对于促卵泡激素分泌的增加、胰岛素抵抗和雄激素的发育暴露被假设在PCOS中起因果作用。在这里，我们绘制了美国国立卫生研究院PCOS表型的欧洲血统女性的常见遗传易感性位点，该表型赋予代谢性疾病以及生殖激素水平的最高风险。在病例对照荟萃分析中发现了3个具有全基因组意义的基因座，其中2个新基因座定位于chr 8p32.1和chr 11p14.1，1个chr 9q22.32基因座在中国PCOS患者中发现。在促卵泡激素B多肽（FSH B）基因区域的相同chr 11 p14.1 SNP rs11031006与PCOS诊断和促黄体生成激素水平密切相关。这些发现暗示了疾病发病机制中的神经内分泌变化。 多囊卵巢综合征是一种高度遗传的复杂生殖疾病，其潜在的遗传因素尚不清楚。Hayes和Urbanek等人在欧洲女性中发现了三个与神经内分泌变化和疾病易感性密切相关的基因座。
Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels. Three loci reach genome-wide significance in the case–control meta-analysis, two novel loci mapping to chr 8p32.1 and chr 11p14.1, and a chr 9q22.32 locus previously found in Chinese PCOS. The same chr 11p14.1 SNP, rs11031006, in the region of the follicle-stimulating hormone B polypeptide (FSHB) gene strongly associates with PCOS diagnosis and luteinizing hormone levels. These findings implicate neuroendocrine changes in disease pathogenesis. Polycystic Ovary Sydrome is a highly heritable, complex reproductive disorder with unknown underlying genetic factors. Here Hayes and Urbanek et al. identify three loci in European women strongly associated with neuroendocrine changes and disease susceptibility.