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PMID: 21151130 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis.

Nature genetics ·Vol. 43 ·No. 1 ·2011-01-00 ·Pages 51-4

Painter JN, Anderson CA, Nyholt DR, Macgregor S, Lin J, Lee SH, Lambert A, Zhao ZZ, Roseman F, Guo Q, Gordon SD, Wallace L, Henders AK, Visscher PM, Kraft P, Martin NG, Morris AP, Treloar SA, Kennedy SH, Missmer SA, Montgomery GW, Zondervan KT

Abstract

Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increased genetic loading among 1,364 cases with moderate to severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for 'all' endometriosis (P = 2.6 × 10⁻⁷, odds ratio (OR) = 1.22, 95% CI 1.13-1.32) and for moderate to severe disease (P = 1.5 × 10⁻⁹, OR = 1.38, 95% CI 1.24-1.53). We replicated rs12700667 in an independent cohort from the United States of 2,392 self-reported, surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 × 10⁻³, OR = 1.17, 95% CI 1.06-1.28), resulting in a genome-wide significant P value of 1.4 × 10⁻⁹ (OR = 1.20, 95% CI 1.13-1.27) for 'all' endometriosis in our combined datasets of 5,586 cases and 9,331 controls. rs12700667 is located in an intergenic region upstream of the plausible candidate genes NFE2L3 and HOXA10.

MeSH Terms
Australia Basic-Leucine Zipper Transcription Factors/genetics Chromosomes, Human, Pair 15/genetics Cohort Studies Endometriosis/genetics Female Genetic Loci Genetic Predisposition to Disease Genome, Human/genetics Genome-Wide Association Study Homeobox A10 Proteins Homeodomain Proteins/genetics Humans Odds Ratio Risk Factors United Kingdom United States
Chemicals
Basic-Leucine Zipper Transcription Factors Homeobox A10 Proteins Homeodomain Proteins NFE2L3 protein, human HOXA10 protein, human
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Painter Jodie N
Molecular Epidemiology, Queensland Institute of Medical Research, Herston, Queensland, Australia. [email protected]
Anderson Carl A
Nyholt Dale R
Macgregor Stuart
Lin Jianghai
Lee Sang Hong
Lambert Ann
Zhao Zhen Z
Roseman Fenella
Guo Qun
Gordon Scott D
Wallace Leanne
Henders Anjali K
Visscher Peter M
Kraft Peter
Martin Nicholas G
Morris Andrew P
Treloar Susan A
Kennedy Stephen H
Missmer Stacey A
Montgomery Grant W
Zondervan Krina T
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.731
Email
[email protected]
Published
2011-01-00
Epub
2010-00-12
Pages
51-4
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC3019124
Subset
IM
Grants
NCI NIH HHS · R01 CA050385 · United States
NCI NIH HHS · P01 CA087969 · United States
Wellcome Trust · WT084766/Z/08/Z · United Kingdom
NIDDK NIH HHS · P01 DK070756 · United States
Howard Hughes Medical Institute · United States
Wellcome Trust · WT91745/Z/10/Z · United Kingdom
NCI NIH HHS · U01 CA098233 · United States
NICHD NIH HHS · R01 HD057210 · United States
Wellcome Trust · 081682 · United Kingdom
NICHD NIH HHS · R01 HD052473 · United States
NCI NIH HHS · R01 CA067262 · United States
Wellcome Trust · 085235 · United Kingdom
Wellcome Trust · 064890 · United Kingdom
Wellcome Trust · 084766 · United Kingdom
NCI NIH HHS · R01 CA049449 · United States
Wellcome Trust · WT085235/Z/08/Z · United Kingdom
External Links
PubMed source DOI: 10.1038/ng.731 PMC Full Text View journal details
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