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