Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans

European Americans ( EA ) have a better antihypertensive response to β‐blockers when compared with African Americans, albeit with some variability. We undertook a genomewide association study to elucidate the underlying genetic determinants in EA contributing to this variability in blood pressure ( BP ) response. A discovery genomewide association study of change in BP post–metoprolol treatment was performed in EA participants ( n  = 201) from the Pharmacogenomic Evaluation of Antihypertensive Responses‐2 (PEAR‐2) study and tested for replication in the atenolol‐treated EA from the PEAR study ( n  = 233). Rs294610 in the FGD 5 , which encodes for FYVE, RhoGEF and PH Domain Containing 5, ( expression quantitative trait loci for FGD 5 in the small intestine) was significantly associated with increased diastolic BP response to β‐blockers in the PEAR‐2 study ( P  = 3.41 × 10 −6 , β = −2.70) and replicated ( P  = 0.01, β = −1.17) in the PEAR study . Post–meta‐analysis of these studies, an additional single nucleotide polymorphism rs45545233 in the SLC 4A1 , encoding for Solute Carrier Family 4 Member 1, ( expression quantitative trait loci for dual specificity phosphatase 3 in the artery tibial) was identified that was significantly associated with a poor response to β‐blockers ( P  = 3.43 × 10 −6 , β = 4.57) and was replicated in the atenolol add‐on cohort ( P  = 0.007, β = 4.97). We identified variants in FGD 5 and SLC 4A1 , which have been previously cited as candidate genes for hypertension, to be associated with a β‐blocker BP response in EA . Further elucidation is warranted of the underlying mechanisms of these variants and genes by which they influence the BP response to β‐blockers.