Abstract P493: A Multivariate Analysis of Genetic Risk Scores for Heart Failure and Left Ventricular Mass Derived From Multi-Ancestry Populations and Left Ventricular Mass Amongst African Americans: The Jackson Heart Study
Authors: Douglas McLaurin, Philip Turk, Olivia Affuso, Elizabeth Heitman, Laura M Raffield
Journal: Circulation (2024)

Background: Increased left ventricular (LV) mass is an outcome of LV remodeling that can result in development of left ventricular hypertrophy (LVH), a maladaptive disorder that increases the risk of heart failure. Elevated LV mass is a sensitive predictor of adverse cardiovascular events. African Americans experience a disproportionate burden of heart failure risk and development of LVH. The influence of genetics on this health disparity is unclear and a topic of interest. Genome-wide association studies (GWAS) have uncovered many variants associated with numerous adverse cardiovascular outcomes, such as heart failure and LV phenotypes. However, the relevance of these studies for African Americans may be limited as these analyses have been conducted in multi-ancestry populations with limited representation of African heritage. The question of whether these genetic risk variants can be used to predict LV phenotypes in an independent African American population remains unanswered. Hypothesis: Variant loci that have been associated with heart failure and LV mass in multi-ancestry populations will be associated with LV mass amongst African Americans in the Jackson Heart Study (JHS). Methods: Thirty-nine (39) SNPs associated with heart failure and ten (10) SNPs associated with LV mass were identified from two published studies in which participants of African ancestry or Black individuals comprised less than 15% and 2%, respectively. Using the published effect size estimates, genetic risk scores (GRSs) for heart failure and LV mass were computed for 2,175 African American participants (mean age 55, 63% female) in the JHS with complete data and consent for genetic research. We assessed the linear association of heart failure and LV mass GRSs with LV mass indexed to height (LVM h ) and indexed to body surface area (LVM bsa ). A multivariate general linear model was fit to both LVM h and LVM bsa containing both GRS predictors and accounting for age, sex, BMI (mean 31.5), diabetes (22%), and hypertension (52%). No multicollinearity was noted among these explanatory variables using variance inflation factors. Due to non-constant error variance, a log transformation was conducted on both LV mass response variables. Type III MANOVA Pillai tests were run to assess the effects of the GRSs on the log LVM bsa and log LVM h values. Conclusion: When accounting for age, BMI, sex, diabetes, and hypertension, we found that neither the heart failure GRS (p-val = 0.4012) nor the LV mass GRS (p-val = 0.8332) had an effect on both log LVM bsa and log LVM h . There is insufficient evidence to suggest that heart failure and LV mass variants derived from predominantly European multi-ancestry populations are linearly associated with log LV mass amongst African Americans in the Jackson Heart Study. Our work highlights the need for greater recruitment and targeted studies of populations with African ancestry for GWAS of LV phenotypes.