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

Nat Commun
Authors
Keywords
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.

Year of Publication
2015
Journal
Nat Commun
Volume
6
Pages
7502
Date Published
2015 Aug 18
ISSN
2041-1723
URL
DOI
10.1038/ncomms8502
PubMed ID
26284813
PubMed Central ID
PMC4557132
Links
Grant list
U10 HD055942 / HD / NICHD NIH HHS / United States
090532 / Wellcome Trust / United Kingdom
U10 HD055944 / HD / NICHD NIH HHS / United States
UL1 TR000150 / TR / NCATS NIH HHS / United States
UL1 TR000430 / TR / NCATS NIH HHS / United States
R01 DK65598 / DK / NIDDK NIH HHS / United States
R01 HL075079 / HL / NHLBI NIH HHS / United States
U10 HD27049 / HD / NICHD NIH HHS / United States
R01 HD29364 / HD / NICHD NIH HHS / United States
R01 HD057223 / HD / NICHD NIH HHS / United States
G9710020 / Medical Research Council / United Kingdom
U10 HD38998 / HD / NICHD NIH HHS / United States
U10 HD055936 / HD / NICHD NIH HHS / United States
U10 HD39005 / HD / NICHD NIH HHS / United States
U10 HD038992 / HD / NICHD NIH HHS / United States
P50 HD044405 / HD / NICHD NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
U54 HD28934 / HD / NICHD NIH HHS / United States
U10 HD38992 / HD / NICHD NIH HHS / United States
P50 HD057796 / HD / NICHD NIH HHS / United States
U10 HD055925 / HD / NICHD NIH HHS / United States
P30 ES013508 / ES / NIEHS NIH HHS / United States
086596 / Wellcome Trust / United Kingdom
R01 HD065029 / HD / NICHD NIH HHS / United States
R01 DK071895 / DK / NIDDK NIH HHS / United States
UL1 RR033184 / RR / NCRR NIH HHS / United States
K24 HD01346 / HD / NICHD NIH HHS / United States
G0802782 / Medical Research Council / United Kingdom
UL1 RR025758 / RR / NCRR NIH HHS / United States
098381 / Wellcome Trust / United Kingdom
R01 HD056510 / HD / NICHD NIH HHS / United States
R01 HD057450 / HD / NICHD NIH HHS / United States
DK20595 / DK / NIDDK NIH HHS / United States
UL1 TR000127 / TR / NCATS NIH HHS / United States
U54 HD34449 / HD / NICHD NIH HHS / United States