title: Consistency of genome-wide associations across major ancestral groups.
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.
authors.affiliation: Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, 45110 Ioannina, Greece.
authors.forename: Evangelia E
authors.initials: EE
authors.lastname: Ntzani
authors.forename: George
authors.initials: G
authors.lastname: Liberopoulos
authors.forename: Teri A
authors.initials: TA
authors.lastname: Manolio
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D044466:Asian People / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: D005819:Genetic Markers