Dataset Information

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]

PMID: 25892113

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Project description:Aims/hypothesisType 2 diabetes is a growing global public health challenge. Investigating quantitative traits, including fasting glucose, fasting insulin and HbA1c, that serve as early markers of type 2 diabetes progression may lead to a deeper understanding of the genetic aetiology of type 2 diabetes development. Previous genome-wide association studies (GWAS) have identified over 500 loci associated with type 2 diabetes, glycaemic traits and insulin-related traits. However, most of these findings were based only on populations of European ancestry. To address this research gap, we examined the genetic basis of fasting glucose, fasting insulin and HbA1c in participants of the diverse Population Architecture using Genomics and Epidemiology (PAGE) Study.MethodsWe conducted a GWAS of fasting glucose (n = 52,267), fasting insulin (n = 48,395) and HbA1c (n = 23,357) in participants without diabetes from the diverse PAGE Study (23% self-reported African American, 46% Hispanic/Latino, 40% European, 4% Asian, 3% Native Hawaiian, 0.8% Native American), performing transethnic and population-specific GWAS meta-analyses, followed by fine-mapping to identify and characterise novel loci and independent secondary signals in known loci.ResultsFour novel associations were identified (p < 5 × 10-9), including three loci associated with fasting insulin, and a novel, low-frequency African American-specific locus associated with fasting glucose. Additionally, seven secondary signals were identified, including novel independent secondary signals for fasting glucose at the known GCK locus and for fasting insulin at the known PPP1R3B locus in transethnic meta-analysis.Conclusions/interpretationOur findings provide new insights into the genetic architecture of glycaemic traits and highlight the continued importance of conducting genetic studies in diverse populations.Data availabilityFull summary statistics from each of the population-specific and transethnic results are available at NHGRI-EBI GWAS catalog ( https://www.ebi.ac.uk/gwas/downloads/summary-statistics ).

Dataset Information

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

Publications

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

Similar Datasets

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