Test for Rare Variants by Environment Interactions

• Activity Number: 618
• Type: Contributed
• Date/Time: Thursday, August 7, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Xinyi Lin*+ and Seunggeun Lee and Michael Wu and Chaolong Wang and Han Chen and Zilin Li and Xihong Lin
• Companies: Harvard School of Public Health and University of Michigan and Fred Hutchinson Cancer Research Center and Harvard School of Public Health and Harvard School of Public Health and Harvard and Harvard School of Public Health
• Keywords: Genetic Epidemiology

Abstract

The analysis of rare variants by environment interactions in sequencing studies is challenging. Current methods for analyzing association of rare variants with traits cannot be readily applied for testing for rare variants by environment interactions, as these methods do not effectively control for the main effects of the rare variants, leading to unstable results and/or inflated Type 1 error rates. We will first analytically study the bias of conventional burden based tests for gene and environment interactions in the presence of rare variants and show the tests can be invalid and result in inflated Type 1 error rates. To overcome these difficulties, we develop the interaction sequence kernel association test (iSKAT) for assessing rare variants by environment association with traits. We demonstrate the performance of iSKAT using simulation studies and data analysis of a candidate gene sequencing study.