Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations
Author(s)
Type
Journal Article
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.
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.
Date Issued
2015-08-18
Date Acceptance
2015-05-14
Citation
Nature Communications, 2015, 6 (7)
ISSN
2041-1723
Publisher
Nature Publishing Group
Journal / Book Title
Nature Communications
Volume
6
Issue
7
Copyright Statement
This work is licensed under a Creative Commons Attribution 4.0
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
License URL
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
MRC
Grant Number
RDD03 79560
G0802782
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
SYNDROME PCOS
SUSCEPTIBILITY LOCI
CHROMOSOME 2P16.3
COMPLEX DISEASES
ANDROGEN EXCESS
QUALITY-CONTROL
EMERGE NETWORK
WOMEN
VARIANTS
IDENTIFICATION
Publication Status
Published
Article Number
ARTN 7502