Genome-Wide Association Study of Beta-Blocker Survival Benefit in Black and White Patients with Heart Failure with Reduced Ejection Fraction
Recommended Citation
Luzum JA, Campos-Staffico AM, Li J, She R, Gui H, Peterson EL, Liu B, Sabbah HN, Donahue MP, Kraus WE, Williams LK, and Lanfear DE. Genome-Wide Association Study of Beta-Blocker Survival Benefit in Black and White Patients with Heart Failure with Reduced Ejection Fraction. Genes (Basel) 2023; 14(11).
Document Type
Article
Publication Date
10-28-2023
Publication Title
Genes (Basel)
Abstract
In patients with heart failure with reduced ejection fraction (HFrEF), individual responses to beta-blockers vary. Candidate gene pharmacogenetic studies yielded significant but inconsistent results, and they may have missed important associations. Our objective was to use an unbiased genome-wide association study (GWAS) to identify loci influencing beta-blocker survival benefit in HFrEF patients. Genetic variant × beta-blocker exposure interactions were tested in Cox proportional hazards models for all-cause mortality stratified by self-identified race. The models were adjusted for clinical risk factors and propensity scores. A prospective HFrEF registry (469 black and 459 white patients) was used for discovery, and linkage disequilibrium (LD) clumped variants with a beta-blocker interaction of p < 5 × 10(-5), were tested for Bonferroni-corrected validation in a multicenter HFrEF clinical trial (288 black and 579 white patients). A total of 229 and 18 variants in black and white HFrEF patients, respectively, had interactions with beta-blocker exposure at p < 5 × 10(-5) upon discovery. After LD-clumping, 100 variants and 4 variants in the black and white patients, respectively, remained for validation but none reached statistical significance. In conclusion, genetic variants of potential interest were identified in a discovery-based GWAS of beta-blocker survival benefit in HFrEF patients, but none were validated in an independent dataset. Larger cohorts or alternative approaches, such as polygenic scores, are needed.
Medical Subject Headings
Humans; Adrenergic beta-Antagonists; Genome-Wide Association Study; Heart Failure; Prospective Studies; Stroke Volume; Ventricular Dysfunction, Left; Black or African American; White
PubMed ID
38002962
Volume
14
Issue
11
