title: Significant evidence of one or more susceptibility loci for endometriosis with near-Mendelian inheritance on chromosome 7p13-15.
abstract: BACKGROUND
  Endometriosis is a common disease with a heritable component. The collaborative International Endogene Study consists of two data sets (Oxford and Australia) comprising 1176 families with multiple affected. The aim was to investigate whether the apparent concentration of cases in a proportion of families could be explained by one or more rare variants with (near-)Mendelian autosomal inheritance.
  
  
  RESULTS
  Linkage analyses (aimed at finding chromosomal regions harbouring disease-predisposing genes) were conducted in families with three or more affected (Oxford: n = 52; Australia: n = 196). In the Oxford data set, a non-parametric linkage score (Kong & Cox (K&C) Log of ODds (LOD)) of 3.52 was observed on chromosome 7p (genome-wide significance P = 0.011). A parametric MOD score (equal to maximum LOD maximized over 357 possible inheritance models) of 3.89 was found at 65.72 cM (D7S510) for a dominant model with reduced penetrance. After including the Australian data set, the non-parametric K&C LOD of the combined data set was 1.46 at 57.3 cM; the parametric analysis found an MOD score of 3.30 at D7S484 (empirical significance: P = 0.035) for a recessive model with high penetrance. Critical recombinant analysis narrowed the probable region of linkage down to overlapping 6.4 Mb and 11 Mb intervals containing 48 and 96 genes, respectively.
  
  
  CONCLUSIONS
  This is the first report to suggest that there may be one or more high-penetrance susceptibility loci for endometriosis with (near-)Mendelian inheritance.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, UK. krinaz@well.ox.ac.uk
authors.forename: Krina T
authors.initials: KT
authors.lastname: Zondervan
authors.forename: Susan A
authors.initials: SA
authors.lastname: Treloar
authors.forename: Jianghai
authors.initials: J
authors.lastname: Lin
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weeks
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
authors.forename: Jon
authors.initials: J
authors.lastname: Mangion
authors.forename: Ian J
authors.initials: IJ
authors.lastname: MacKay
authors.forename: Lon R
authors.initials: LR
authors.lastname: Cardon
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Kennedy
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
mesh_terms: D001315:Australia; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004715:Endometriosis / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D010641:Phenotype; D006113:United Kingdom