Human Genetics

, Volume 131, Issue 7, pp 1057–1071 | Cite as

Consistency of genome-wide associations across major ancestral groups

  • Evangelia E. Ntzani
  • George Liberopoulos
  • Teri A. Manolio
  • John P. A. IoannidisEmail author
Original Investigation


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.


Standardize Mean Difference African Ancestry Ancestral Origin Ancestral Group Ancestry Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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


Han Chinese in Beijing


Confidence interval


Genome-wide association study


Genome-wide significance


Inter-quartile range


Japanese in Tokyo


Linkage disequilibrium


National Centre for Biotechnology Information


National Human Genome Research Institute


Odds ratio


PubMed identification number


Relative odds ratio


Standardized mean difference


Single nucleotide polymorphism


Yoruba in Ibadan


Conflict of interest

The authors declare no conflict of interest related to this manuscript.

Supplementary material

439_2011_1124_MOESM1_ESM.doc (36 kb)
Supplementary Methods and Appendix A (DOC 36 kb)
439_2011_1124_MOESM2_ESM.doc (115 kb)
Supplementary Table 1 (DOC 115 kb)
439_2011_1124_MOESM3_ESM.doc (106 kb)
Supplementary Table 2 (DOC 106 kb)
439_2011_1124_MOESM4_ESM.doc (164 kb)
Supplementary Table 3 (DOC 164 kb)
439_2011_1124_MOESM5_ESM.doc (266 kb)
Supplementary Figure (DOC 266 kb)
439_2011_1124_MOESM6_ESM.doc (17 kb)
Supplementary Table 4 (DOC 17.4 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Evangelia E. Ntzani
    • 1
  • George Liberopoulos
    • 1
  • Teri A. Manolio
    • 2
  • John P. A. Ioannidis
    • 1
    • 3
    • 4
    Email author
  1. 1.Clinical and Molecular Epidemiology Unit, Department of Hygiene and EpidemiologyUniversity of Ioannina School of MedicineIoanninaGreece
  2. 2.Office of Population GenomicsNational Human Genome Research InstituteBethesdaUSA
  3. 3.Department of Medicine, Stanford Prevention Research CenterStanford University School of MedicineStanfordUSA
  4. 4.Department of Health Research and PolicyStanford University School of MedicineStanfordUSA

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