Abstract
Genome-wide association studies (GWAS) have revealed important links between genetic markers across the human genome and phenotypic traits, including risk factors for disease. Studies have shown that GWAS continue to be overwhelmingly conducted on people of primarily European descent, despite the fact that the vast majority of human genomic variation is present in non-European populations such as those in Africa. To enhance our understanding of diversity in the pharmacogenomics and precision medicine literature, this review provides a window into the representation of biogeographical populations that have been studied for pharmacogenetic traits, such as enzyme metabolism and adverse drug response. Using the Medical Subject Headings (MeSH) ontology search terms in PubMed, studies were identified that are either population-based, or include a description of the study population on the basis of biological or environmental diversity. The results of this scoping review indicate that the majority of relevant papers (>95% of studies tagged in PubMed with MeSH terms “precision medicine” or “pharmacogenetics”, N=23,701) are not annotated with the “population group” MeSH term, suggesting that the majority of studies in this literature are not population-based, or the authors chose not to describe the study population. Among those studies related to pharmacogenetics or precision medicine that are specific to human population groups (N=1006) and were included in the analysis after filtering and screening on eligibility criteria (N=192), the majority of single-population studies included individuals of African, Asian, and European origins, or genetic ancestry. Combining studies of single and multiple populations, 33% involve participants of Asian origin or ancestry; 30% European; 24% African; 10% Hispanic or Latino; and < 3% American Indian or Alaska Native. These data provide a baseline for future comparison, indicating which biogeographic groups have informed the pharmacogenomic knowledgebase specific to diverse human populations. Challenges and potential solutions to improve diversity in the field and in genetics research more broadly are discussed.
Acknowledgments
The author would like to thank Arturo Lopez Pineda for discussions and advice regarding the methods and visualization of a scoping review, and Genevieve Wojcik, Ragan Hart, and Carlos Bustamante for comments and feedback on early stages of review methods, findings, and figures.
Abbreviations
GWAS, Genome-wide association studies; SNP, single-nucleotide polymorphism; ELSI, ethical, legal, social implications; MRCA, most recent common ancestor; LD, linkage disequilibrium; AIMs, ancestry informative markers; PCA, principal components analysis; GxG, gene-gene interactions; GxE, gene-environment interactions; 1KG, 1000 Genomes Project; HGDP, Human Genome Diversity Project; AME, American; EAS, East Asian; EUR, European; SAS, Central/South Asian; NEA, Near Eastern; OCE, Oceanian; SSA, Sub-Saharan African; AAC, African American/Afro-Caribbean, LAT, Latino; NIH, National Institutes of Health; EBI-EMBL, European Biomedical Informatics Institute; NSF, National Science Foundation.
Disclosure
The author reports no conflicts of interest in this work.