Genome‐Wide Association Approach Identified Novel Genetic Predictors of Heart Rate Response to β‐Blockers

• Published in: Journal of the American Heart Association 2018-03, Vol.7 (5), p.n/a
• Main Authors: Shahin, Mohamed H., Conrado, Daniela J., Gonzalez, Daniel, Gong, Yan, Lobmeyer, Maximilian T., Beitelshees, Amber L., Boerwinkle, Eric, Gums, John G., Chapman, Arlene, Turner, Stephen T., Cooper‐DeHoff, Rhonda M., Johnson, Julie A.
• Format: Article
• Language: English
• Subjects: atenolol; heart rate; metoprolol; Original Research; pharmacogenomics; β‐blockers
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.117.006463

Background For many indications, the negative chronotropic effect of β‐blockers is important to their efficacy, yet the heart rate (HR) response to β‐blockers varies. Herein, we sought to use a genome‐wide association approach to identify novel single nucleotide polymorphisms (SNPs) associated with HR response to β‐blockers. Methods and Results We first performed 4 genome‐wide association analyses for HR response to atenolol (a β1‐adrenergic receptor blocker) as: (1) monotherapy or (2) add‐on therapy, in 426 whites and 273 blacks separately from the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) study. A meta‐analysis was then performed between the genome‐wide association analysis performed in PEAR atenolol monotherapy and add‐on therapy, in each race separately, using the inverse variance method assuming fixed effects. From this analysis, SNPs associated with HR response to atenolol at a P