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

Stat Biosci. 2018 Apr;10(1):117-138. doi: 10.1007/s12561-017-9189-9. Epub 2017 Mar 24.


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.

Keywords: IBS kernel; correlated binary responses; generalized estimating equations; kernel machine; nonparametric regression.