Genomewide
linkage study in 1,176 affected sister pair families
identifies a significant susceptibility locus for endometriosis
on chromosome 10q26
The cause of endometriosis remains uncertain despite
>50 years of hypothesis-driven research, and thus
the therapeutic options are limited.
Disease predisposition is inherited as a complex genetic
trait, which provides an alternative route to understanding
the disease.
The International Endogene Study, headed by Stephen
Kennedy and Grant Montgomery from Oxford University,
England, sought to identify susceptibility loci, using
a positional-cloning approach that starts with linkage
analysis to identify genomic regions likely to harbor
these genes.
They conducted a linkage study of 1,176 families (931
from an Australian group and 245 from a UK group), each
with at least two members - mainly affected sister pairs
- with surgically diagnosed disease. They identified
a region of significant linkage on chromosome 10q26
(maximum LOD score [MLS] of 3.09; genomewide P = .047)
and another region of suggestive linkage on chromosome
20p13 (MLS = 2.09). Minor peaks (with MLS > 1.0)
were found on chromosomes 2, 6, 7, 8, 12, 14, 15, and
17.
This is the first report of linkage to a major locus
for endometriosis. The findings will facilitate discovery
of novel positional genetic variants that influence
the risk of developing this debilitating disease. Greater
understanding of the aberrant cellular and molecular
mechanisms involved in the aetiology and pathophysiology
of endometriosis should lead to better diagnostic methods
and targeted treatments.
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