Computationally Efficient Rare Variant Association Testing in Multi-Ethnic Cohorts with Large-Scale Sequencing Data

• Activity Number: 390 - Challenges in Whole-Genome Sequence Analysis: Experiences and Approaches in the TOPMed Project
• Type: Invited
• Date/Time: Tuesday, August 1, 2017 : 2:00 PM to 3:50 PM
• Sponsor: WNAR
• Author(s): Timothy Thornton*
• Companies: University of Washington
• Keywords: Sequencing ; Association testing ; Population Structure ; Admixture ; Relatedness ; Rare Variants

Abstract

TOPMed includes samples from multi-ethnic cohorts, and there is great potential that the whole genome sequencing data generate for TOPMED will provide new insights into the contributions of both common and rare genetic variants to human health as well health disparities. The complex genetic diversity among sampled individuals in TOPMed, however, poses special challenges, and currently, there is a dearth of statistical methods available for appropriate analysis of sequencing data from ancestrally diverse populations. In this talk, we propose computationally efficient statistical methods for association testing using large-scale sequencing data from multi-ethnic cohorts. The methodology is appropriate for samples with complex structure, including cryptic relatedness, population structure and/or ancestry admixture. We demonstrate the utility of the methods in applications to phenotypes in TOPMed.