Seminars

General Departmental Seminar Series

Detecting Linkage Adaptive to Linkage Disequilibrium

Jian Huang, Department of Statistics and Actuarial Science, University of Iowa

Friday, October 13th, 2000, 12:00-1:00 pm

K6/124 Clinical Science Center, 600 Highland Avenue

ABSTRACT

Due to rapid advancements in molecular technology, it is becoming feasible in the near future to use the single- nucleotide polymorphism (SNP) markers in a genome screen. With a dense SNP map, some of the markers could be in linkage disequilibrium (LD) with the disease-predisposing alleles. Significant LD may also result from other factors such as admixture of two or more subpopulations differing in allele frequencies. However, in practice, the extent of LD between a marker and disease is usually unknown. Therefore, it is of interest to develop linkage analysis methods that are adaptive to LD. We consider a modified LOD score method for testing linkage that incorporates LD (LD-LOD). By examination of its score statistic, we show that the LD-LOD score method adaptively combines two sources of information: (a) the IBD sharing score which is informative for linkage regardless of the existence of LD; and (b) the contrast between allele-specific IBD sharing scores which is informative for linkage only in the presence of LD. In particular, we show that, for triad data, a simple recessive LD-LOD test is asymptotically equivalent to the TDT; and for ASP data, it is an adaptive combination of the TDT and the ASP mean test. We demonstrate that the LD-LOD score method has relatively good statistical efficiency in comparison with the ASP mean test and the TDT for a broad range of LD and the genetic models we considered. Therefore, the LD-LOD score method is an interesting approach for detecting linkage when the extent of LD is unknown.

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