Family-Based Rare Variant Association Analysis: A Fast and Efficient Method of Multivariate Phenotype Association Analysis.

TitleFamily-Based Rare Variant Association Analysis: A Fast and Efficient Method of Multivariate Phenotype Association Analysis.
Publication TypeJournal Article
Year of Publication2016
AuthorsWang, L, Lee, S, Gim, J, Qiao, D, Cho, M, Elston, RC, Silverman, EK, Won, S
JournalGenet Epidemiol
Volume40
Issue6
Pagination502-11
Date Published2016 09
ISSN1098-2272
KeywordsComputer Simulation, Genetic Association Studies, Genetic Variation, Humans, Likelihood Functions, Models, Genetic, Phenotype
Abstract

Family-based designs have been repeatedly shown to be powerful in detecting the significant rare variants associated with human diseases. Furthermore, human diseases are often defined by the outcomes of multiple phenotypes, and thus we expect multivariate family-based analyses may be very efficient in detecting associations with rare variants. However, few statistical methods implementing this strategy have been developed for family-based designs. In this report, we describe one such implementation: the multivariate family-based rare variant association tool (mFARVAT). mFARVAT is a quasi-likelihood-based score test for rare variant association analysis with multiple phenotypes, and tests both homogeneous and heterogeneous effects of each variant on multiple phenotypes. Simulation results show that the proposed method is generally robust and efficient for various disease models, and we identify some promising candidate genes associated with chronic obstructive pulmonary disease. The software of mFARVAT is freely available at http://healthstat.snu.ac.kr/software/mfarvat/, implemented in C++ and supported on Linux and MS Windows.

DOI10.1002/gepi.21985
Alternate JournalGenet. Epidemiol.
PubMed ID27312886
PubMed Central IDPMC4981535
Grant ListR01 HL113264 / HL / NHLBI NIH HHS / United States
U54 HG006493 / HG / NHGRI NIH HHS / United States
R01 HL075478 / HL / NHLBI NIH HHS / United States
P01 HL105339 / HL / NHLBI NIH HHS / United States
K01 HL129039 / HL / NHLBI NIH HHS / United States