title: High-density fine-mapping of a chromosome 10q26 linkage peak suggests association between endometriosis and variants close to CYP2C19.
abstract: OBJECTIVE
  To refine a previously reported linkage peak for endometriosis on chromosome 10q26, and conduct follow-up analyses and a fine-mapping association study across the region to identify new candidate genes for endometriosis.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Academic research.
  
  
  METHODS
  Cases=3,223 women with surgically confirmed endometriosis; controls=1,190 women without endometriosis and 7,060 population samples.
  
  
  METHODS
  Analysis of 11,984 single nucleotide polymorphisms on chromosome 10.
  
  
  METHODS
  Allele frequency differences between cases and controls.
  
  
  RESULTS
  Linkage analyses on families grouped by endometriosis symptoms (primarily subfertility) provided increased evidence for linkage (logarithm of odds score=3.62) near a previously reported linkage peak. Three independent association signals were found at 96.59 Mb (rs11592737), 105.63 Mb (rs1253130), and 124.25 Mb (rs2250804). Analyses including only samples from linkage families supported the association at all three regions. However, only rs11592737 in the cytochrome P450 subfamily C (CYP2C19) gene was replicated in an independent sample of 2,079 cases and 7,060 population controls.
  
  
  CONCLUSIONS
  The role of the CYP2C19 gene in conferring risk for endometriosis warrants further investigation.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland, Australia. jodie.painter@qimr.edu.au
authors.forename: Jodie N
authors.initials: JN
authors.lastname: Painter
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
authors.forename: Andrew
authors.initials: A
authors.lastname: Morris
authors.forename: Zhen Z
authors.initials: ZZ
authors.lastname: Zhao
authors.forename: Anjali K
authors.initials: AK
authors.lastname: Henders
authors.forename: Ann
authors.initials: A
authors.lastname: Lambert
authors.forename: Leanne
authors.initials: L
authors.lastname: Wallace
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Kennedy
authors.forename: Susan A
authors.initials: SA
authors.lastname: Treloar
authors.forename: Krina T
authors.initials: KT
authors.lastname: Zondervan
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D065731:Cytochrome P-450 CYP2C19; D004715:Endometriosis / Q000201:enzymology / Q000235:genetics*; D004739:England; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011793:Queensland; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19