Cardiorenal Genomics for Risk Prediction in African Descent Populations
Approved Research ID: 63682
Approval date: January 25th 2021
Hypertension (HTN) and chronic kidney disease (CKD) are major risk factors for cardiovascular disease outcomes which disproportionately affect African Americans (AAs). AAs have a higher prevalence of HTN and CKD (40%, 18%, respectively) than EAs (28%, 13%, respectively) and Hispanics (26%, 15%, respectively), and are also more likely to be taking antihypertensives (AHT), yet are less likely to have their blood pressure (BP) controlled. The reasons for these differences are known to include both environmental and inherited factors. To date, environmental contributors are better understood, yet few clinically impactful genetic-risk contributors overburdening AAs have been identified. Some examples include apolipoprotein L1 (APOL1; risk variants G1 and G2 confer up to a 7-fold increased risk for end-stage renal disease), Sickle Cell Trait (HBB rs344 associated with a 2-fold increased risk for end-stage renal disease), and TTR V122I (associated with 2 fold higher odds for heart failure).
Overall, more research is needed to continue to characterize genetic risk factors that can help explain and ultimately prevent these disparities. Unfortunately, populations of African ancestry have been severely underrepresented in genetic epidemiology and pharmacogenetic research (AAs represent <5% of the individuals covered in published genome wide association studies (GWAS) leaving many suspected gaps).Recently, this problem has gained increasing recognition due advancements in genetic testing (that has been severely biased towards European Ancestry (EAs) populations due to the available data (e.g. the UK Biobank >400K EAs, <15K AAs). Overall, this research will aid in filling in major gaps in genetic research in this ancestry group. We expect replication efforts from Aims 1-2 to be complete in the next 2 years and for aim 3 in the year 3.