Significant evidence of one or more susceptibility loci for endometriosis with near-Mendelian inheritance on chromosome 7p13-15

December 2006

Research published in Human Reproduction by the collaborative International Endogene Study suggests that there may be one or more high-penetrance susceptibility loci for endometriosis with (near-)Mendelian inheritance.

The collaborative International Endogene Study consists of two data sets (Oxford and Australia) comprising 1176 families with multiple affecteds.

The aim of the research team 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.

Linkage analyses (aimed at finding chromosomal regions harbouring disease-predisposing genes) were conducted in families with three or more affected women with endometriosis. (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.

Source

Zondervan KT, Treloar SA, Lin J, Weeks DE, Nyholt DR, Mangion J, Mackay IJ, Cardon LR, Martin NG, Kennedy SH, Montgomery GW.Significant evidence of one or more susceptibility loci for endometriosis with near-Mendelian inheritance on chromosome 7p13-15. Hum Reprod 2006 Dec 11; [Epub ahead of print]