Using Imputed Genotype Data in Joint Score Tests for Genetic Association and Gene-Environment Interactions in Case-Control Studies

• Activity Number: 107
• Type: Invited
• Date/Time: Monday, August 10, 2015 : 8:30 AM to 10:20 AM
• Sponsor: Biometrics Section
• Author(s): Nilanjan Chatterjee and Minsun Song*
• Companies: National Cancer Institute and National Cancer Institute
• Keywords: case-control studies ; restrospective likelihood ; prospective-likelihood ; empirical-Bayes

Abstract

Genome-wide association studies (GWAS) are now routinely imputed for untyped SNPs with powerful tools such as IMPUTE2 up to various reference panels such as Hapmap2 or 1000Genome. The use of predicted allele count for imputed SNPs as the dosage variable is known to produce valid score-test for simple genetic association. In this report, we investigate how to best handle imputed SNPs in various modern complex tests for genetic associations incorporating gene-environment interactions. In particular, we focus on case-control association studies where inference in an underlying logistic regression model can be performed using various alternative methods that rely on varying degree on an assumption of gene-environment independence in the underlying population. As increasingly large scale GWAS are being performed through consortia effort where it is preferable to share only summary-level information across studies, we also explore how these methods could be implemented in the context of meta-analysis.