title: Sequence Kernel Association Test of Multiple Continuous Phenotypes.
abstract: Genetic studies often collect multiple correlated traits, which could be analyzed jointly to increase power by aggregating multiple weak effects and provide additional insights into the etiology of complex human diseases. Existing methods for multiple trait association tests have primarily focused on common variants. There is a surprising dearth of published methods for testing the association of rare variants with multiple correlated traits. In this paper, we extend the commonly used sequence kernel association test (SKAT) for single-trait analysis to test for the joint association of rare variant sets with multiple traits. We investigate the performance of the proposed method through extensive simulation studies. We further illustrate its usefulness with application to the analysis of diabetes-related traits in the Atherosclerosis Risk in Communities (ARIC) Study. We identified an exome-wide significant rare variant set in the gene YAP1 worthy of further investigations.
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Baolin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000465:Algorithms; D000704:Analysis of Variance; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics*; D059472:Exome; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008957:Models, Genetic; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human
keywords: GWAS; SKAT; rare variant; score statistic