Finding Rare Variants Affecting Disease Risk

• Activity Number: 100
• Type: Invited
• Date/Time: Monday, August 2, 2010 : 8:30 AM to 10:20 AM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Kathryn Roeder*+
• Companies: Carnegie Mellon University

Abstract

Sequencing can be used to discover genes with rare variants that affect complex phenotypes. A complication is that a variant may be neutral, risk, or protective. We propose testing for the presence of this mixture of effects across a set of rare variants in a gene. However, this test is sensitive to differences in ancestry of cases and controls. PCA is routinely used to summarize the genetic similarity between subjects. The eigenvectors are interpreted as dimensions of ancestry. We build on this idea using a spectral graph approach that produces more meaningful delineation of ancestry. Once an eigenmap is constructed, new individuals can be projected onto the map based on their genotypes. This provides a tool for selecting controls from available sources with ancestry matched to cases, thus avoiding confounding in our tests for the effect of rare variants on a phenotype.