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Sequence Kernel Association Test of Multiple Continuous Phenotypes.

TitleSequence Kernel Association Test of Multiple Continuous Phenotypes.
Publication TypeJournal Article
Year of Publication2016
AuthorsWu B
Secondary AuthorsPankow JS
JournalGenet Epidemiol
Volume40
Issue2
Pagination91-100
Date Published2016 Feb
ISSN1098-2272
KeywordsAdaptor Proteins, Signal Transducing, Algorithms, Analysis of Variance, Atherosclerosis, Exome, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Models, Genetic, Phenotype, Phosphoproteins, Quantitative Trait, Heritable, Transcription Factors
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.

DOI10.1002/gepi.21945
Alternate JournalGenet Epidemiol
PubMed ID26782911
PubMed Central IDPMC4724299
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201000010C / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
5RC2HL102419 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
R01 CA134848 / CA / NCI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
GM083345 / GM / NIGMS NIH HHS / United States
CA134848 / CA / NCI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
R01 GM083345 / GM / NIGMS NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
HHSN268201000012C / HL / NHLBI NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States