Integrating Family-Specific Linkage Scores in Case-Control Tests of Association

• Activity Number: 664
• Type: Invited
• Date/Time: Thursday, August 8, 2013 : 10:30 AM to 12:20 PM
• Sponsor: WNAR
• Author(s): Tasha E. Fingerlin*+ and Anna L. Peljto and Sharon Lutz
• Companies: University of Colorado Anschutz Medical Campus and University of Colorado Anschutz Medical Campus and Univ. of Colorado
• Keywords: statistical genetics ; rare variant ; case-control

Abstract

Risk of most complex diseases is likely determined by multiple genetic variants, non-genetic factors, and their interactions. Multiple study designs are used to identify genetic risk variants; familial linkage and unrelated case-control studies are common. A priority for current studies is to examine rare variants via sequencing studies, often combining a subset of the familial cases from linkage studies with unrelated cases and controls. Tests of association for rare variants have been developed in the case-control setting, where the variants are aggregated to improve power. However, none use family-specific linkage information. We present methodology to directly combine family-specific linkage information with other case-control data to identify genetic risk variants. We propose extensions of case-control tests of association that require only one case per family, use external measures of allele sharing from linkage studies, and allow joint analysis of familial cases with linkage information and other cases. We compare the type I error and power of these tests to those that ignore family-specific linkage information to give guidance on when the new tests are preferable.