Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations

M. Geoffrey Hayes(Northwestern University), Margrit Urbanek(Northwestern University), David A. Ehrmann(University of Chicago), Loren L. Armstrong(Northwestern University), Ji Young Lee(Northwestern University), Ryan Sisk(Northwestern University), Tugce Karaderi(Centre for Human Genetics), Thomas M. Barber(University of Warwick), Mark I. McCarthy(Centre for Human Genetics), Stephen Franks(Hammersmith Hospital), Cecilia M. Lindgren(Centre for Human Genetics), Corrine K. Welt(University of Utah), Evanthia Diamanti‐Kandarakis(National and Kapodistrian University of Athens), Dimitrios Panidis(Aristotle University of Thessaloniki), Mark O. Goodarzi(Cedars-Sinai Medical Center), Ricardo Azziz(Augusta University), Yi Zhang(Medical College of Wisconsin), Roland James(Medical College of Wisconsin), Michael Olivier(Texas Biomedical Research Institute), Ahmed H. Kissebah(Medical College of Wisconsin), Reproductive Medicine Network(University of Colorado Anschutz Medical Campus), Ruben Alvero(Duke University), Huiman X. Barnhart(Duke University), Valerie L. Baker(University of Pennsylvania), Kurt T. Barnhart(University of Alabama at Birmingham), G. Wright Bates(The University of Texas at San Antonio Health Science Center), Robert G. Brzyski(The University of Texas at San Antonio Health Science Center), Bruce R. Carr(Baylor College of Medicine), Sandra Ann Carson(University of Vermont), Peter R. Casson(University of Vermont), Nicholas A. Cataldo(University of Michigan), Gregory M. Christman(University of Michigan), Christos Coutifaris(Wayne State University), Michael P. Diamond(Wayne State University), Esther Eisenberg(University of Pittsburgh), Gabriella G. Gosman(University of Pittsburgh), Linda C. Giudice(University of California, San Francisco), Daniel J. Haisenleder(Yale University), Hao Huang(Wayne State University), Stephen A. Krawetz(Virginia Commonwealth University), Scott Lucidi(Virginia Commonwealth University), Peter G. McGovern(Duke Medical Center), Evan R. Myers(Virginia Commonwealth University), John E. Nestler(Virginia Commonwealth University), Dana A. Ohl(University of Michigan), Nanette Santoro(University of Colorado Anschutz Medical Campus), William D. Schlaff(University of Colorado Anschutz Medical Campus), Peter J. Snyder(University of Alabama at Birmingham), Michael P. Steinkampf(SUNY Upstate Medical University), J.C. Trussell(SUNY Upstate Medical University), Rebecca Usadi(Carolinas Medical Center), Qingshang Yan(Yale University), Heping Zhang(Karolinska Institutet), Elisabet Stener‐Victorin(Karolinska Institutet), Richard S. Legro(Northwestern University), Andrea Dunaif(Northwestern University)
Nature Communications
August 18, 2015
10.1038/ncomms8502
Cited by 541Open Access
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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 [Corrected] 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.

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