{"doi":"10.3390/genes14112019","title":"Genome-Wide Association Study of Beta-Blocker Survival Benefit in Black and White Patients with Heart Failure with Reduced Ejection Fraction","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.","journal":"Genes","year":2023,"id":373722,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":743418,"name":"Alessandra M. Campos‐Staffico","orcid":"0000-0003-4172-7524","position":1,"is_corresponding":false},{"id":736533,"name":"Jia Li","orcid":"0000-0002-1353-7347","position":2,"is_corresponding":false},{"id":471326,"name":"Ruicong She","orcid":"0000-0002-5087-9362","position":3,"is_corresponding":false},{"id":218533,"name":"Hongsheng Gui","orcid":"0000-0002-0460-7446","position":4,"is_corresponding":false},{"id":250999,"name":"Edward L. Peterson","orcid":"0000-0002-3546-3828","position":5,"is_corresponding":false},{"id":637001,"name":"Bin Liu","orcid":"0000-0003-2184-4723","position":6,"is_corresponding":false},{"id":280683,"name":"Hani N. Sabbah","orcid":"0000-0002-2850-6105","position":7,"is_corresponding":false},{"id":611416,"name":"Mark Donahue","orcid":null,"position":8,"is_corresponding":false},{"id":231464,"name":"William E. Kraus","orcid":"0000-0003-1930-9684","position":9,"is_corresponding":false},{"id":24921,"name":"L. Keoki Williams","orcid":"0000-0002-7592-5791","position":10,"is_corresponding":false},{"id":382886,"name":"David E. Lanfear","orcid":"0000-0001-6471-1483","position":11,"is_corresponding":false},{"id":302261,"name":"Jasmine A. Luzum","orcid":"0000-0003-3639-717X","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:16:07.080027Z","pmid":"38002962","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}