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

Nat Commun 2015 Aug 18;6:7502. Epub 2015 Aug 18.

1] Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA [2] Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms8502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557132PMC
August 2015
110 Reads

Publication Analysis

Top Keywords

chr 11p141
8
ovary syndrome
8
luteinizing hormone
8
follicle-stimulating hormone
8
polycystic ovary
8
hormone levels
8
european ancestry
8
pcos
5
hormone
5
risk metabolic
4
phenotype confers
4
confers highest
4
highest risk
4
morbidities well
4
three loci
4
loci reach
4
reach genome-wide
4
levels three
4
reproductive hormone
4
pcos phenotype
4

References

(Supplied by CrossRef)

E Diamanti-Kandarakis et al.
Endocr. Rev. 2012

S Franks et al.
Hum. Reprod. Update 2008

CA Eagleson et al.
J. Clin. Endocrinol. Metab. 2000

DH Abbott et al.
J. Endocrinol. 2002

EB Johnstone et al.
J. Clin. Endocrinol. Metab. 2010

BC Fauser et al.
Hum. Reprod. Update 2008

R Azziz et al.
J. Clin. Endocrinol. Metab. 2006

BC Fauser et al.
Fertil. Steril. 2012

RS Legro et al.
Proc. Natl Acad. Sci. USA 1998

S Franks et al.
J. Clin. Endocrinol. Metab. 2008

Similar Publications