Author:
Hayes M. Geoffrey, ,Urbanek Margrit,Ehrmann David A.,Armstrong Loren L.,Lee Ji Young,Sisk Ryan,Karaderi Tugce,Barber Thomas M.,McCarthy Mark I.,Franks Stephen,Lindgren Cecilia M.,Welt Corrine K.,Diamanti-Kandarakis Evanthia,Panidis Dimitrios,Goodarzi Mark O.,Azziz Ricardo,Zhang Yi,James Roland G.,Olivier Michael,Kissebah Ahmed H.,Stener-Victorin Elisabet,Legro Richard S.,Dunaif Andrea
Abstract
Abstract
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 8p23.1 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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