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Consistency of genome-wide associations across major ancestral groups

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Abstract

It is not well known whether genetic markers identified through genome-wide association studies (GWAS) confer similar or different risks across people of different ancestry. We screened a regularly updated catalog of all published GWAS curated at the NHGRI website for GWAS-identified associations that had reached genome-wide significance (p ≤ 5 × 10−8) in at least one major ancestry group (European, Asian, African) and for which replication data were available for comparison in at least two different major ancestry groups. These groups were compared for the correlation between and differences in risk allele frequencies and genetic effects’ estimates. Data on 108 eligible GWAS-identified associations with a total of 900 datasets (European, n = 624; Asian, n = 217; African, n = 60) were analyzed. Risk-allele frequencies were modestly correlated between ancestry groups, with >10% absolute differences in 75–89% of the three pairwise comparisons of ancestry groups. Genetic effect (odds ratio) point estimates between ancestry groups correlated modestly (pairwise comparisons’ correlation coefficients: 0.20–0.33) and point estimates of risks were opposite in direction or differed more than twofold in 57%, 79%, and 89% of the European versus Asian, European versus African, and Asian versus African comparisons, respectively. The modest correlations, differing risk estimates, and considerable between-association heterogeneity suggest that differential ancestral effects can be anticipated and genomic risk markers may need separate further evaluation in different ancestry groups.

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Abbreviations

CEU:

Utah residents with Northern and Western European ancestry from the CEPH collection

CHB:

Han Chinese in Beijing

CI:

Confidence interval

GWAS:

Genome-wide association study

GWS:

Genome-wide significance

IQR:

Inter-quartile range

JPT:

Japanese in Tokyo

LD:

Linkage disequilibrium

NCBI:

National Centre for Biotechnology Information

NHGRI:

National Human Genome Research Institute

OR:

Odds ratio

PMID:

PubMed identification number

ROR:

Relative odds ratio

SMD:

Standardized mean difference

SNP:

Single nucleotide polymorphism

YRI:

Yoruba in Ibadan

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Authors and Affiliations

  1. Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, 45110, Ioannina, Greece

    Evangelia E. Ntzani, George Liberopoulos & John P. A. Ioannidis

  2. Office of Population Genomics, National Human Genome Research Institute, Bethesda, MD, 20892-2152, USA

    Teri A. Manolio

  3. Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, 94305-5411, USA

    John P. A. Ioannidis

  4. Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, 94305-5411, USA

    John P. A. Ioannidis

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  1. Evangelia E. Ntzani
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  2. George Liberopoulos
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  3. Teri A. Manolio
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  4. John P. A. Ioannidis
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Correspondence to John P. A. Ioannidis.

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Ntzani, E.E., Liberopoulos, G., Manolio, T.A. et al. Consistency of genome-wide associations across major ancestral groups. Hum Genet 131, 1057–1071 (2012). https://doi.org/10.1007/s00439-011-1124-4

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  • DOI: https://doi.org/10.1007/s00439-011-1124-4

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