Replication and Analysis of Complex Trait Rare Variant Association Studies

• Activity Number: 275
• Type: Invited
• Date/Time: Tuesday, August 2, 2011 : 8:30 AM to 10:20 AM
• Sponsor: ENAR
• Author(s): Suzanne Margaret Leal*+
• Companies: Baylor College of Medicine
• Keywords: rare variants ; sequence data ; association analysis ; replication ; genetics

Abstract

There is overwhelming evidence that rare variants play an important role in complex disease etiology. Currently many studies are generating exome sequence data using next generation sequencing in order to detect rare variant complex trait associations. Association methods used to analyze common variants should not be used for the analysis or rare variants since they are grossly underpowered. Instead methods which have been developed to test for association with rare variants which rely on aggregating information on rare variants within a region, e.g. gene should be used. Once associations are detected it is important to replicate the findings in an independent sample, since findings can be false positives even if the family wise error rate is well controlled. Spurious associations can occur due to improperly controlling for population admixture/substructure and sequencing errors. Methods to analyze rare variant association data for complex traits will be presented and their power will be compared for a variety of underlying genetic models. Additionally strategies for gene-based replication will be compared