@article{9afac4cf2a684ab89468691390bf96e0,
title = "Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations",
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 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.",
author = "Hayes, {M. Geoffrey} and Margrit Urbanek and Ehrmann, {David A.} and Armstrong, {Loren L.} and Lee, {Ji Young} and Ryan Sisk and Tugce Karaderi and Barber, {Thomas M.} and McCarthy, {Mark I.} and Stephen Franks and Lindgren, {Cecilia M.} and Welt, {Corrine K.} and Evanthia Diamanti-Kandarakis and Dimitrios Panidis and Goodarzi, {Mark O.} and Ricardo Azziz and Yi Zhang and James, {Roland G.} and Michael Olivier and Kissebah, {Ahmed H.} and Elisabet Stener-Victorin and Legro, {Richard S.} and Andrea Dunaif and Ruben Alvero and Barnhart, {Huiman X.} and Valerie Baker and Barnhart, {Kurt T.} and Bates, {G. Wright} and Brzyski, {Robert G.} and Carr, {Bruce R.} and Carson, {Sandra A.} and Peter Casson and Cataldo, {Nicholas A.} and Gregory Christman and Christos Coutifaris and Diamond, {Michael P.} and Esther Eisenberg and Gosman, {Gabriella G.} and Giudice, {Linda C.} and Haisenleder, {Daniel J.} and Hao Huang and Krawetz, {Stephen A.} and Scott Lucidi and McGovern, {Peter G.} and Myers, {Evan R.} and Nestler, {John E.} and Dana Ohl and Nanette Santoro and Schlaff, {William D.} and Peter Snyder and Steinkampf, {Michael P.} and Trussell, {J. C.} and Rebecca Usadi and Qingshang Yan and Heping Zhang",
note = "Funding Information: This study was supported by US National Institutes of Health (NIH) grants R01 HD057223 (A.D.), P50 HD044405 (A.D.), U54 HD34449 (A.D.), R01 HD057450 (M.U.), and R01 HD056510 (R.S.L.), R01 HL075079 (D.A.E), P50 HD057796 (D.A.E.), R01 HD065029 (C.K.W.), R01 HD29364 (R.A.), K24 HD01346 (R.A.), R01 DK071895 (A.H.K.), R01 DK65598 (A.H.K.), Wellcome Trust grants 090532 (M.I.M.), 098381 (M.I.M.) and 086596 (C.M.L.), MRC Programme grants G9710020 (S.F. and M.I.M.) and G0802782 (S.F.), as well as The University of Chicago Diabetes Research and Training Centre DK20595 (D.A.E.), Award 1-10-CT-57 from the American Diabetes Association (C.K.W.), and by TOPS (Take Off Pounds Sensibly) Club, Inc.. Partial funding for the clinical studies was provided by UL1 TR000150, UL1 RR033184, UL1 TR000430 and UL1 RR025758 from the National Centre for Advancing Translational Sciences. This study makes use of GWAS data generated by the Wellcome Trust Case-Control consortium 2 (WTCCC2) UK controls from the 1958 British Birth Cohort. The NIH Cooperative Multicenter Reproductive Medicine Network includes the following Members of the Steering Committee and Grant Numbers: Grants U10 HD27049 (Christos Coutifaris, University of Pennsylvania, Philadelphia, PA), U10 HD38992 (Richard S. Legro, Penn State College of Medicine, Hershey, PA), U10 HD055925 (Heping Zhang, Yale University, New Haven, CT), U10 HD39005 (Michael P Diamond, Wayne State University, Detroit, MI), U10 HD38998 (William D. Schlaff, University of Colorado, Denver, CO), U10 HD055936 (Gregory M. Christman, University of Michigan, Ann Arbor, MI), U10 HD055942 (Robert G Bryzski, University of Texas at San Antonio, San Antonio, TX), and U10 HD055944 (Peter R Casson, University of Vermont, Burlington VT), Chair of the Steering Committee: Nanette Santoro, University of Colorado, Denver CO and Program Officer, Esther Eisenberg, Eunice Kennedy Shriver NICHD.) Some hormone assays were performed at the University of Virginia Centre for Research in Reproduction Ligand Assay and Analysis Core that is supported by U54 HD28934 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = aug,
day = "18",
doi = "10.1038/ncomms8502",
language = "English (US)",
volume = "6",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}