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

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 affecteds. The aim was to investigate whether the apparent concentration of cases in a propo...

Full description

Saved in:
Bibliographic Details
Published in:Human reproduction (Oxford) 2007-03, Vol.22 (3), p.717-728
Main Authors: Zondervan, Krina T., Treloar, Susan A., Lin, Jianghai, Weeks, Daniel E., Nyholt, Dale R., Mangion, Jon, MacKay, Ian J., Cardon, Lon R., Martin, Nicholas G., Kennedy, Stephen H., Montgomery, Grant W.
Format: Article
Language:English
Subjects:
Australia
Biological and medical sciences
chromosome 7
Chromosomes, Human, Pair 7 - genetics
endometriosis
Endometriosis - genetics
family study
Female
Genetic Linkage
Genetic Predisposition to Disease - genetics
Gynecology. Andrology. Obstetrics
Haplotypes
Humans
linkage
Lod Score
Medical sciences
Phenotype
United Kingdom
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 affecteds. 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. METHODS AND 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.
ISSN:0268-1161
1460-2350
DOI:10.1093/humrep/del446