Transethnic differences in GWAS signals: A simulation study.
Ann Hum Genet
; 82(5): 280-286, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-29733446
ABSTRACT
Genome-wide association studies (GWASs) have allowed researchers to identify thousands of single nucleotide polymorphisms (SNPs) and other variants associated with particular complex traits. Previous studies have reported differences in the strength and even the direction of GWAS signals across different populations. These differences could be due to a combination of (1) lack of power, (2) allele frequency differences, (3) linkage disequilibrium (LD) differences, and (4) true differences in causal variant effect sizes. To determine whether properties (1)-(3) on their own might be sufficient to explain the patterns previously noted in strong GWAS signals, we simulated case-control data of European, Asian and African ancestry, applying realistic allele frequencies and LD from 1000 Genomes data but enforcing equal causal effect sizes across populations. Much of the observed differences in strong GWAS signals could indeed be accounted for by allele frequency and LD differences, enhanced by the Euro-centric SNP bias and lower SNP coverage found in older GWAS panels. While we cannot rule out a role for true transethnic effect size differences, our results suggest that strong causal effects may be largely shared among human populations, motivating the use of transethnic data for fine-mapping.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desequilíbrio de Ligação
/
Polimorfismo de Nucleotídeo Único
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Estudo de Associação Genômica Ampla
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Frequência do Gene
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Ann Hum Genet
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos