title: Similarity-based multimarker association tests for continuous traits.
abstract: Testing multiple markers simultaneously not only can capture the linkage disequilibrium patterns but also can decrease the number of tests and thus alleviate the multiple-testing penalty. If a gene is associated with a phenotype, subjects with similar genotypes in this gene should also have similar phenotypes. Based on this concept, we have developed a general framework that is applicable to continuous traits. Two similarity-based tests (namely, SIMc and SIMp tests) were derived as special cases of the general framework. In our simulation study, we compared the power of the two tests with that of the single-marker analysis, a standard haplotype regression, and a popular and powerful kernel machine regression. Our SIMc test outperforms other tests when the average R(2) (a measure of linkage disequilibrium) between the causal variant and the surrounding markers is larger than 0.3 or when the causal allele is common (say, frequency = 0.3). Our SIMp test outperforms other tests when the causal variant was introduced at common haplotypes (the maximum frequency of risk haplotypes >0.4). We also applied our two tests to an adiposity data set to show their utility.
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, USA.
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Lin
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Tiwari
authors.forename: Guimin
authors.initials: G
authors.lastname: Gao
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.forename: John J
authors.initials: JJ
authors.lastname: Arcaroli
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.forename: Nianjun
authors.initials: N
authors.lastname: Liu
mesh_terms: D050154:Adiposity / Q000235:genetics; D003201:Computers; D056726:Genetic Association Studies / Q000379:methods*; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D015233:Models, Statistical
chemical_list: D005819:Genetic Markers