Meta‐Analysis of Rare Variant Association Tests in Multiethnic Populations

In this study, we compare the performance of several statistical approaches for assessing rare variant associations across multiple ethnicities. We also explore how different ethnic sampling fractions perform, including single‐ethnicity studies and studies that sample up to four ethnicities. We conducted simulations based on targeted sequencing data from 4,611 women in four ethnicities (African, European, Japanese American, and Latina). As with single‐ethnicity studies, burden tests had greater power when all causal rare variants were deleterious, and variance component‐based tests had greater power when some causal rare variants were deleterious and some were protective. Multiethnic studies had greater power than single‐ethnicity studies at many loci, with inclusion of African Americans providing the largest impact. On average, studies including African Americans had as much as 20% greater power than equivalently sized studies without African Americans. This suggests that association studies between rare variants and complex disease should consider including subjects from multiple ethnicities, with preference given to genetically diverse groups.

Source: Genetic Epidemiology - December 7, 2015 Category: Epidemiology Authors: Akweley Mensah‐Ablorh, Sara Lindstrom, Christopher A. Haiman, Brian E. Henderson, Loic Le Marchand, Seunngeun Lee, Daniel O. Stram, A. Heather Eliassen, Alkes Price, Peter Kraft Tags: Research Article Source Type: research