Identify Rare Variants Underlying Complex Disease Through a Family-Based Association Design

• Activity Number: 623
• Type: Contributed
• Date/Time: Thursday, August 2, 2012 : 8:30 AM to 10:20 AM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Jin Zhou*+ and Nan Laird
• Companies: Harvard University and Harvard University
• Keywords: Family-based association test ; linear mixed model ; next-generation sequencing ; rare variants

Abstract

Rapid advances in sequencing technologies provide opportunities for identifying rare variants associated with complex diseases. However, such studies usually suffer from limited testing power due to low allele frequencies as well as lack of methodologies for adjusting population stratification. We propose here a powerful testing strategy to test for association between genetic variants (common and rare) in a region and a continuous or dichotomous trait through a family-based design, which is robust to population stratification. The strategy is based on a transmission test combined with a linear mixed model. It not only inherits all the merits of family-based tests but also allows the disease variants to be both protective and risk predisposing. Different weighting schemes can also be incorporated for power boosting. Through analysis of simulated data, we show that our method is powerful across a wide range of practical scenarios and has comparable power with population based rare variant test.