A multimarker regression-based test of linkage for affected sib-pairs at two linked loci.

Abstract:

:We address the analytical problem of evaluating the evidence for linkage at a test locus while taking into account the effect of a known linked disease locus. The method we propose is a multimarker regression approach that models the identity-by-descent states for affected sib-pairs at a series of linked markers in terms of the identity-by-descent state at the known disease locus. Our method allows analysis to be performed at a test location (or a series of locations) without the requirement that identity-by-descent be directly observed at either the test or the known conditioning locus. An advantage of our method is that identity-by-descent states from multiple markers are included simultaneously in the test of linkage, without recourse to multipoint imputation. The properties and power of the method are examined under various null and alternative hypotheses. The method is applied to data from a study of 1,056 type 1 diabetes families to examine the evidence for an additional putative locus (IDDM15) on chromosome 6q, linked to IDDM1 in the HLA region on chromosome 6p. After accounting for the strong effect of IDDM1 and the differing rates of male and female recombination in the region, we find only marginal evidence for IDDM15 (P = 0.03 to 0.002, using different methods) approximately 15 cM centromeric of the original localisation.

journal_name

Genet Epidemiol

journal_title

Genetic epidemiology

authors

Barber MJ,Todd JA,Cordell HJ

doi

10.1002/gepi.20137

subject

Has Abstract

pub_date

2006-04-01 00:00:00

pages

191-208

issue

3

eissn

0741-0395

issn

1098-2272

journal_volume

30

pub_type

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