Genetic Matching for Robust and Powerful Detection of Gene-Gene Interactions in Case-Control Studies

• Activity Number: 418
• Type: Contributed
• Date/Time: Tuesday, August 3, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Samsiddhi Bhattacharjee*+ and Nilanjan Chatterjee
• Companies: National Cancer Institute and National Cancer Institute
• Keywords: Gene-Gene Interaction ; Epistasis ; Population Stratification ; Genetic Matching ; Conditional Logistic ; Case-Control

Abstract

The case-only approach for detecting interactions makes a crucial assumption of gene-gene independence for physically distant genes. While this strategy provides considerable power improvement, it is prone to significant bias when the independence assumption is violated. We propose a robust yet powerful approach that uses fine-matching of individuals based on their genetic ancestry, as inferred from principal components of genome-wide null markers. Matched pairs are analyzed using extensions of conditional logistic regression that derive additional power from a weak gene-gene independence assumption. We compare our methods to existing approaches analytically and using simulations. We also discuss possible statistical and computational strategies to further improve power of matching-based methods.