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Leveraging Multi-ethnic Evidence for Mapping Complex Traits in Minority Populations: An Empirical Bayes Approach.


ABSTRACT: Elucidating the genetic basis of complex traits and diseases in non-European populations is particularly challenging because US minority populations have been under-represented in genetic association studies. We developed an empirical Bayes approach named XPEB (cross-population empirical Bayes), designed to improve the power for mapping complex-trait-associated loci in a minority population by exploiting information from genome-wide association studies (GWASs) from another ethnic population. Taking as input summary statistics from two GWASs-a target GWAS from an ethnic minority population of primary interest and an auxiliary base GWAS (such as a larger GWAS in Europeans)-our XPEB approach reprioritizes SNPs in the target population to compute local false-discovery rates. We demonstrated, through simulations, that whenever the base GWAS harbors relevant information, XPEB gains efficiency. Moreover, XPEB has the ability to discard irrelevant auxiliary information, providing a safeguard against inflated false-discovery rates due to genetic heterogeneity between populations. Applied to a blood-lipids study in African Americans, XPEB more than quadrupled the discoveries from the conventional approach, which used a target GWAS alone, bringing the number of significant loci from 14 to 65. Thus, XPEB offers a flexible framework for mapping complex traits in minority populations.

SUBMITTER: Coram MA 

PROVIDER: S-EPMC4570551 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Leveraging Multi-ethnic Evidence for Mapping Complex Traits in Minority Populations: An Empirical Bayes Approach.

Coram Marc A MA   Candille Sophie I SI   Duan Qing Q   Chan Kei Hang K KH   Li Yun Y   Kooperberg Charles C   Reiner Alex P AP   Tang Hua H  

American journal of human genetics 20150416 5


Elucidating the genetic basis of complex traits and diseases in non-European populations is particularly challenging because US minority populations have been under-represented in genetic association studies. We developed an empirical Bayes approach named XPEB (cross-population empirical Bayes), designed to improve the power for mapping complex-trait-associated loci in a minority population by exploiting information from genome-wide association studies (GWASs) from another ethnic population. Tak  ...[more]

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