Diversity In Precision Medicine And Pharmacogenetics: Methodological And Conceptual Considerations For Broadening Participation

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.

Keywords: GWAS; biogeographic populations; genomic variation; population groups; representation; scoping review.

Figure 1

Scoping Review Flow Chart. The stages of a scoping review are highlighted, with the number of items evaluated at each step: 1) Identification of articles matching specified Mesh terms in PubMed (N=1,006); 2) Screening of articles using filters for availability and relevance (N=202); 3) Determination of eligibility by additional inclusion/exclusion criteria (N=192); and 4) Characteristics of articles included after the first three steps of identification, screening, and eligibility. These characteristics include whether studies were conducted on a single or multiple population(s), and the number of studies conducted in different biogeographical groups, as measured by ancestral origin or socio-cultural label of the population(s) studied.

Figure 2

Global Concentrations of Studies by Country of First Author Affiliation. Heat map shows the number of studies included in this scoping review that were conducted in each country, as determined by the location of the first author’s affiliated institution.

Figure 3

Ancestral Populations Included in Reviewed Research by Geographical Region of First Author Affiliation. For each study, geographical region was determined by pooling countries of first author affiliations into broad continental categories. Each study received a binary indicator of whether or not it included at least one population from each broad ancestral category, so studies with more than one study population received more than one indicator. Therefore, the total number on the Y-axis does not reflect the number of studies, but rather the distribution of populations studied within each geographic region. This graph thus illustrates the representation of ancestral populations in the body of research produced in each of the continental regions of the world.

Figure 4

Populations Studied in Research Conducted in North America. Among articles included in the scoping review that had first author affiliations in North America (N=102), this figure illustrates which study populations were involved, both as single-population studies and combined in multiple-population studies. In contrast to Figure 3, which shows the total number of populations studied, this pie chart shows the distribution and combination(s) of those populations included across the total number of studies conducted in North America.