Genomics and Biobank Research for Health Equity

National Institute On Minority Health And Health Disparities

Investigators

Linked publications, trials & patents

Abstract

Today we are starting to fulfill the promise of genomics for personalized medicine and healthcare. Interestingly, and for a variety of reasons, publicly funded databases continue to miss a vast portion of the world's genetic variation. As of January 2018, the GWAS catalog has registered 78% of individuals from European ancestry while underrepresented populations make up less than 4% including African (2.4%), Hispanic or Latin American (1.3%) and Native American (0.03%). The sampling bias is referred to as the genomics research gap and has the potential to exacerbate existing health disparities among underrepresented and underserved populations. Populations underrepresented in biomedical research bear a disproportionate burden for many diseases, including diabetes type 2. This is particularly true for Native American communities in the US, who have among the lowest levels of participation in genomic studies seen for any ethnic group. Genomic studies must be more representative of all populations so that all people can benefit from the upcoming genomic revolution in healthcare. We are interested in studying how combinations of genetic ancestry in admixed Latin American populations may impact genomic determinants of health and disease. We have found ancestry-enriched SNPs in Latin American populations having a substantial effect on health- and disease-related phenotypes. In a recent study we focused on C-reactive protein (CRP), which is synthesized by hepatocytes and secreted to the bloodstream in response to inflammation. CRP is employed as a serum biomarker for both acute and chronic inflammation, with important implications for immune response and overall health. Elevated levels of CRP have been shown to be associated with an increased risk of diabetes, cardiovascular disease, psychological stress, and all-cause mortality. Here we compared the contributions of genetic ancestry, socioenvironmental factors, and inflammation-related health conditions to ethnic differences in C-reactive protein levels. We used multivariable regression to compare CRP blood serum levels between Black and White ethnic groups from the United Kingdom Biobank (UKBB) prospective cohort study. CRP serum levels are significantly associated with ethnicity in an age and sex adjusted model. Study participants who identify as Black have higher average CRP than those who identify as White, CRP increases with age, and females have higher average CRP than males. Ethnicity and sex show a significant interaction effect on CRP. Black females have higher average CRP levels than White females, whereas White males have higher average CRP than Black males. Significant associations between CRP, ethnicity, and genetic ancestry are almost completely attenuated in a fully adjusted model that includes socioenvironmental factors and inflammation-related health conditions. BMI, smoking, and socioeconomic deprivation all have high relative effects on CRP. These results indicate that socioenvironmental factors contribute more to CRP ethnic differences than genetics. Differences in CRP are associated with ethnic disparities for a number of chronic diseases, including type 2 diabetes, essential hypertension, sarcoidosis, and lupus erythematosus. Our results indicate that ethnic differences in CRP are linked to both socioenvironmental factors and numerous ethnic health disparities. Our group is also developing algorithms and software for local and global ancestry estimation that scale well with biobank data and are actively maintaining a repository on GitHub: https://github.com/healthdisparities.