Genetic risk prediction in Hispanics/Latinos: milestones, challenges, and social-ethical considerations

Abstract

Genome-wide association studies (GWAS) have allowed the identification of disease-associated variants, which can be leveraged to build polygenic scores (PGSs). Even though PGSs can be a valuable tool in personalized medicine, their predictive power is limited in populations of non-European ancestry, particularly in admixed populations. Recent efforts have focused on increasing racial and ethnic diversity in GWAS, thus, addressing some of the limitations of genetic risk prediction in these populations. Even with these efforts, few studies focus exclusively on Hispanics/Latinos. Additionally, Hispanic/Latino populations are often considered a single population despite varying admixture proportions between and within ethnic groups, diverse genetic heterogeneity, and demographic history. Combined with highly heterogeneous environmental and socioeconomic exposures, this diversity can reduce the transferability of genetic risk prediction models. Given the recent increase of genomic studies that include Hispanics/Latinos, we review the milestones and efforts that focus on genetic risk prediction, summarize the potential for improving PGS transferability, and highlight the challenges yet to be addressed. Additionally, we summarize social-ethical considerations and provide ideas to promote genetic risk prediction models that can be implemented equitably.

Keywords: Genomic studies; Health disparities; Hispanics; Latin Americans; Latinos; Personalized medicine; Polygenic risk scores; Polygenic scores.

Fig. 1

Percent of Hispanics/Latinos included in the Polygenic Score (PGS) Catalog. Estimation of Hispanics/Latinos included in discovery and/or training and evaluation samples in the Polygenic Score Catalog (PGS). Percentages were calculated by totaling the number of either polygenic scores (PGSs) or traits that specifically included the term Hispanics or Latinos in either discovery or training samples, and evaluation samples