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 Epidemioljournal_title
Genetic epidemiologyauthors
Barber MJ,Todd JA,Cordell HJdoi
10.1002/gepi.20137subject
Has Abstractpub_date
2006-04-01 00:00:00pages
191-208issue
3eissn
0741-0395issn
1098-2272journal_volume
30pub_type
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pub_type: 杂志文章
doi:10.1002/gepi.1370030102
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pub_type: 杂志文章
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pub_type: 杂志文章
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