Analysis of left ventricular mass for African American individuals using multi-ancestry polygenic risk scores: the Jackson Heart Study

Open Heart. 2025 Nov 27;12(2):e003501. doi: 10.1136/openhrt-2025-003501.

Abstract

Background: Left ventricular mass (LVM) is suggested to be a sensitive predictor of adverse cardiovascular outcomes, such as heart failure. In recent years, genome-wide association studies have discovered loci that associate with outcomes related to LVM, providing an opportunity for the development of genetic risk scores. However, the relevance of these genetic variants to non-European ancestry groups requires additional testing. Here, we examined if variants that have been associated with heart failure and LVM in multi-ancestry populations are associated with LVM among African American individuals in the Jackson Heart Study (JHS).

Methods: Heart failure and LVM associated variants were identified from two published multi-ancestry studies. Two polygenic risk scores (PRSs) were computed for 2175 African American participants (mean age 53, 63% female). We assessed the linear association of both PRSs with LVM indexed to height (LVMh) and indexed to body surface area (LVMbsa) and fit a multivariate general linear model to LVM containing both PRS and covariates (age, sex, body mass index (BMI), diabetes and hypertension). Type III MANOVA Pillai tests were run to assess the effects of the PRS on the log LVM values.

Results: Linear correlation analysis showed positive associations between age and LVMh (r=0.278) and LVMbsa (r=0.296) as well as BMI with LVMh (r=0.320). A strong linear correlation was observed between LVMh and LVMbsa (r=0.894). Elevated LVM among individuals with diabetes and hypertension was observed. When accounting for age, sex, BMI, diabetes and hypertension, we found insufficient evidence to suggest that the heart failure PRS affected either measure of LVM; the same can be said for the LVM PRS.

Conclusion: We find insufficient evidence to suggest that heart failure and LVM genetic variants derived from predominantly European multi-ancestry populations are linearly associated with log LVM among African American participants in the JHS.

Keywords: Epidemiology; Genetic Association Studies; Heart Failure; Risk Factors.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Black or African American* / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genetic Risk Score
  • Genome-Wide Association Study
  • Heart Failure* / diagnosis
  • Heart Failure* / ethnology
  • Heart Failure* / genetics
  • Heart Ventricles* / diagnostic imaging
  • Heart Ventricles* / physiopathology
  • Humans
  • Hypertrophy, Left Ventricular* / diagnosis
  • Hypertrophy, Left Ventricular* / ethnology
  • Hypertrophy, Left Ventricular* / genetics
  • Hypertrophy, Left Ventricular* / physiopathology
  • Male
  • Middle Aged
  • Mississippi / epidemiology
  • Multifactorial Inheritance*
  • Phenotype
  • Risk Assessment / methods
  • Risk Factors
  • White