Health Disparities in Cardiometabolic Traits: Genomics, Gaps, and Paradoxes

Abstract

Cardiometabolic traits vary considerably across ancestry groups, creating interest in disentangling the contributing factors to minimize health disparities. While environmental factors, such as socioeconomic status, access to healthcare, and lifestyle, are expected to play a large role in these differences, the contribution of genomics is less clear. This presentation will consider health disparities in cardiometabolic traits and the role of genomics can play in disentangling or exacerbating these disparities, with examples drawn from serum lipids and African ancestry populations. Serum lipids (especially HDL cholesterol and triglycerides) manifest clear differences in distribution across ancestries. While individuals of African ancestry often experience worse cardiometabolic outcomes (e.g., higher rates of hypertension, obesity, and diabetes), healthier mean serum lipid concentrations are generally observed among those of African ancestry. This lipid profile persists in those of West African ancestry across the African Diaspora, despite differences in social factors and lifestyle, lending support to genomic influences. This distribution, however, does not translate into a reduced rate of lipids‐associated cardiometabolic diseases, for reasons which are unclear, and this discrepancy has implications for use of lipid biomarkers for identifying individuals with disease risk. Well‐powered genomic studies of serum lipids in African ancestry individuals are emerging, revealing novel loci along with some evidence of gene‐lifestyle interactions and differing associations among subcontinental groups. These studies, along with increasing publications of other cardiometabolic traits in African and other non‐European ancestry individuals, are of great importance in a field plagued by underrepresentation of non‐European ancestry individuals. This underrepresentation has profound implications for the clinical utility of genomic discoveries. Without attention to this issue, genomics is poised to exacerbate health disparities in non‐EUR ancestry groups. African ancestry individuals are poorly represented in key genomic databases, yet their profound genetic diversity makes it likely to find variants among them that are not present in other populations. This imbalance can lead to clinical care that is sub‐optimal for those of African ancestry compared to better‐represented groups, a rising concern with increasing use of genomics in clinical decisions. For example, polygenic risk scores, derived from large, well‐powered GWAS, can predict disease risk for some traits of a magnitude that rivals Mendelian risk transmission, growing closer to clinical utility. Unfortunately, because of the comparatively limited representation of non‐European ancestry individuals in the underlying GWAS, these tools perform more poorly in these individuals. While these findings call for a greater number of genomic studies in diverse populations, attention also must be paid to the way individuals of non‐European ancestry are included and presented to ensure that the results facilitate the advancements their inclusion can address. Genomics has the potential to promote understanding of health disparities, but care must be given that they do not play a role in exacerbating them.