A Powerful Test for SNP Effects on Multivariate Binary Outcomes using Kernel Machine Regression.

TitleA Powerful Test for SNP Effects on Multivariate Binary Outcomes using Kernel Machine Regression.
Publication TypeJournal Article
Year of Publication2018
AuthorsDavenport, Clemontina A., Arnab Maity, Patrick F. Sullivan, and Jung-Ying Tzeng
JournalStat Biosci
Volume10
Issue1
Pagination117-138
Date Published2018 Apr
ISSN1867-1764
Abstract

Evaluating multiple binary outcomes is common in genetic studies of complex diseases. These outcomes are often correlated because they are collected from the same individual and they may share common marker effects. In this paper, we propose a procedure to test for effect of a SNP-set on multiple, possibly correlated, binary responses. We develop a score-based test using a nonparametric modeling framework that jointly models the global effect of the marker set. We account for the nonlinear effects and potentially complicated interaction between markers using reproducing kernels. Our testing procedure only requires estimation under the null hypothesis and we use multivariate generalized estimating equations (GEEs) to estimate the model components to account for the correlation among the outcomes. We evaluate finite sample performance of our test via simulation study and demonstrated our methods using the CATIE antibody study data and the CoLaus Study data.

DOI10.1007/s12561-017-9189-9
Alternate JournalStat Biosci
Original PublicationA powerful test for SNP effects on multivariate binary outcomes using kernel machine regression.
PubMed ID30420901
PubMed Central IDPMC6226013
Grant ListP01 CA142538 / CA / NCI NIH HHS / United States
R00 ES017744 / ES / NIEHS NIH HHS / United States
R01 MH084022 / MH / NIMH NIH HHS / United States
Project: