An Overview of Strategies for Detecting Genotype-Phenotype Associations Across Ancestrally Diverse Populations

Genome-wide association studies (GWAS) have been very successful at identifying genetic variants influencing a large number of traits. Although the great majority of these studies have been performed in European-descent individuals, it has been recognised that including populations with differing ancestries enhances the potential for identifying causal SNPs due to their differing patterns of linkage disequilibrium. However, when individuals from distinct ethnicities are included in a GWAS, it is necessary to implement a number of control steps to ensure that the identified associations are real genotype-phenotype relationships. In this Review, we discuss the analyses that are required when performing multi-ethnic studies, including methods for determining ancestry at the global and local level for sample exclusion, controlling for ancestry in association testing, and post-GWAS interrogation methods such as genomic control and meta-analysis. We hope that this overview provides a primer for those researchers interested in including distinct populations in their studies.

Automated summary

Including populations with differing ancestries in GWAS studies enhances the potential for identifying causal SNPs due to their differing patterns of linkage disequilibrium. However, implementing control steps is necessary to ensure that the identified associations are real genotype-phenotype relationships. Methods for determining ancestry, controlling for ancestry in association testing, and post-GWAS interrogation methods such as genomic control and meta-analysis are essential in multi-ethnic studies.