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

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  • M. Geoffrey Hayes
  • Margrit Urbanek
  • David A. Ehrmann
  • Loren L. Armstrong
  • Ji Young Lee
  • Ryan Sisk
  • Thomas M. Barber
  • Mark I. McCarthy
  • Stephen Franks
  • Cecilia M. Lindgren
  • Corrine K. Welt
  • Evanthia Diamanti-Kandarakis
  • Dimitrios Panidis
  • Mark O. Goodarzi
  • Ricardo Azziz
  • Roland G. James
  • Michael Olivier
  • Ahmed H. Kissebah
  • Elisabet Stener-Victorin
  • Richard S. Legro
  • Andrea Dunaif
  • Ruben Alvero
  • Huiman X. Barnhart
  • Valerie Baker
  • Kurt T. Barnhart
  • G. Wright Bates
  • Robert G. Brzyski
  • Bruce R. Carr
  • Sandra A. Carson
  • Peter Casson
  • Nicholas A. Cataldo
  • Gregory Christman
  • Christos Coutifaris
  • Michael P. Diamond
  • Esther Eisenberg
  • Gabriella G. Gosman
  • Linda C. Giudice
  • Daniel J. Haisenleder
  • Hao Huang
  • Stephen A. Krawetz
  • Scott Lucidi
  • Peter G. McGovern
  • Evan R. Myers
  • John E. Nestler
  • Dana Ohl
  • Nanette Santoro
  • William D. Schlaff
  • Peter Snyder

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.

OriginalsprogEngelsk
Artikelnummer7502
TidsskriftNature Communications
Vol/bind6
ISSN2041-1723
DOI
StatusUdgivet - 18 aug. 2015
Eksternt udgivetJa

ID: 226395787