title: Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis.
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.
authors.affiliation: Molecular Epidemiology, Queensland Institute of Medical Research, Herston, Queensland, Australia. jodie.painter@qimr.edu.au
authors.forename: Jodie N
authors.initials: JN
authors.lastname: Painter
authors.forename: Carl A
authors.initials: CA
authors.lastname: Anderson
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
authors.forename: Stuart
authors.initials: S
authors.lastname: Macgregor
authors.forename: Jianghai
authors.initials: J
authors.lastname: Lin
authors.forename: Sang Hong
authors.initials: SH
authors.lastname: Lee
authors.forename: Ann
authors.initials: A
authors.lastname: Lambert
authors.forename: Zhen Z
authors.initials: ZZ
authors.lastname: Zhao
authors.forename: Fenella
authors.initials: F
authors.lastname: Roseman
authors.forename: Qun
authors.initials: Q
authors.lastname: Guo
authors.forename: Scott D
authors.initials: SD
authors.lastname: Gordon
authors.forename: Leanne
authors.initials: L
authors.lastname: Wallace
authors.forename: Anjali K
authors.initials: AK
authors.lastname: Henders
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.forename: Susan A
authors.initials: SA
authors.lastname: Treloar
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Kennedy
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Missmer
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Krina T
authors.initials: KT
authors.lastname: Zondervan
mesh_terms: D001315:Australia; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D015331:Cohort Studies; D004715:Endometriosis / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D016017:Odds Ratio; D012307:Risk Factors; D006113:United Kingdom; D014481:United States
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C117963:NFE2L3 protein, human; C069634:HOXA10 protein, human