Inference on phenotype-specific effects of genes using multivariate kernel machine regression

Genetic Epidemiology
Arnab MaityJung-Ying Tzeng

Abstract

We consider the problem of assessing the joint effect of a set of genetic markers on multiple, possibly correlated phenotypes of interest. We develop a kernel machine based multivariate regression framework, where the joint effect of the marker set on each of the phenotypes is modeled using prespecified kernel functions with unknown variance components. Unlike most existing methods that mainly focus on the global association between the marker set and the phenotype set, we develop estimation and testing procedures to study phenotype-specific associations. Specifically, we develop an estimation method based on the penalized likelihood approach to estimate phenotype-specific effects and their corresponding standard errors while accounting for possible correlation among the phenotypes. We develop testing procedures for the association of the marker set with any subset of phenotypes using a score-based variance components testing method. We assess the performance of our proposed methodology via a simulation study and demonstrate the utility of the proposed method using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) data.

References

Sep 21, 2005·The New England Journal of Medicine·Jeffrey A LiebermanUNKNOWN Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators
Apr 28, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Richard S E KeefeJeffrey A Lieberman
Feb 7, 2008·American Journal of Human Genetics·Lydia Coulter KweeMichael P Epstein
Mar 19, 2008·Molecular Psychiatry·P F SullivanS L Close
Aug 6, 2009·Journal of the Korean Statistical Society·Wensheng Zhu, Heping Zhang
Jun 22, 2010·American Journal of Human Genetics·Michael C WuXihong Lin
Jul 9, 2011·American Journal of Human Genetics·Michael C WuXihong Lin
Aug 18, 2012·Genetic Epidemiology·Arnab MaityJun-Ying Tzeng
Mar 9, 2013·Genetic Epidemiology·Michael C WuPaul M Armistead
Jul 23, 2015·Genetic Epidemiology·Zhiyuan XuUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Jan 20, 2016·Genetic Epidemiology·Baolin Wu, James S Pankow
Mar 5, 2016·American Journal of Human Genetics·K Alaine BroadawayMichael P Epstein

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