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GENETICS OF HEART RATE OBSERVATIONAL STUDY (GENHRATE)
685 JACC March 21, 2017 Volume 69, Issue 11
Heart Failure and Cardiomyopathies GENETICS OF HEART RATE OBSERVATIONAL STUDY (GENHRATE) Moderated Poster Contributions Heart Failure and Cardiomyopathies Moderated Poster Theater, Poster Hall, Hall C Saturday, March 18, 2017, 12:30 p.m.-12:40 p.m. Session Title: Put Your Codon! Genetic Insights Into Heart Failure Abstract Category: 12. Heart Failure and Cardiomyopathies: Basic Presentation Number: 1226M-03 Authors: Kaleigh L. Evans, Heidi Wirtz, Jia Li, Ruicong She, Juan Maya, Christophe Depre, Andrew Hamer, David Lanfear, Henry Ford Hospital, Detroit, MI, USA, Amgen, Thousand Oaks, CA, USA Background: Elevated heart rate (HR) is a risk factor and therapeutic target in patients with heart failure and reduced ejection fraction (HFrEF). The goal of this study was to assess race and genetic influences on HR in HFrEF.
Methods: Patients who met Framingham criteria for HF, had EF<50%, and self-identified as African American (AA) or white were prospectively enrolled (2007-2015, n=1059). Subjects underwent genome-wide genotyping with which we estimated heritability of resting HR, and then performed genome-wide association study (GWAS) adjusted for race using EMMAX. Heritability p<0.05 was considered significant. GWAS significance was considered at p<5x10-8.
Results: Resting HR was 2 bpm lower in AA vs white patients (70 vs 72.4 bpm, p=0.004). Heritability of HR was high among AA patients (h2 =1, p=0.00048) but not statistically significant among white patients (h2 =0.05, p=0.48). The GWAS results are shown in the figure; one SNP on chromosome (chr) 22 (rs535263906) met genome-wide significance (p=3.3 x 10-8), while two others on chr 6 (rs149447933) and chr 5 (rs541284506) were borderline (p=7.5 x 10-8 and p=9.5 x 10-8, respectively). The chr 22 SNP lies in the gene CELSR1, which is a cadherin and appears to be expressed in cardiac and smooth muscle. Conclusions: Our data suggest that Race and genetics impact HR in HFrEF patients, and identify a novel genetic locus influencing HR in CELSR1. Additional study is needed to better understand the relationship of race and genetics on HR as a treatment target in HFrEF.
Heart Failure and Cardiomyopathies GENETICS OF HEART RATE OBSERVATIONAL STUDY (GENHRATE) Moderated Poster Contributions Heart Failure and Cardiomyopathies Moderated Poster Theater, Poster Hall, Hall C Saturday, March 18, 2017, 12:30 p.m.-12:40 p.m. Session Title: Put Your Codon! Genetic Insights Into Heart Failure Abstract Category: 12. Heart Failure and Cardiomyopathies: Basic Presentation Number: 1226M-03 Authors: Kaleigh L. Evans, Heidi Wirtz, Jia Li, Ruicong She, Juan Maya, Christophe Depre, Andrew Hamer, David Lanfear, Henry Ford Hospital, Detroit, MI, USA, Amgen, Thousand Oaks, CA, USA Background: Elevated heart rate (HR) is a risk factor and therapeutic target in patients with heart failure and reduced ejection fraction (HFrEF). The goal of this study was to assess race and genetic influences on HR in HFrEF.
Methods: Patients who met Framingham criteria for HF, had EF<50%, and self-identified as African American (AA) or white were prospectively enrolled (2007-2015, n=1059). Subjects underwent genome-wide genotyping with which we estimated heritability of resting HR, and then performed genome-wide association study (GWAS) adjusted for race using EMMAX. Heritability p<0.05 was considered significant. GWAS significance was considered at p<5x10-8.
Results: Resting HR was 2 bpm lower in AA vs white patients (70 vs 72.4 bpm, p=0.004). Heritability of HR was high among AA patients (h2 =1, p=0.00048) but not statistically significant among white patients (h2 =0.05, p=0.48). The GWAS results are shown in the figure; one SNP on chromosome (chr) 22 (rs535263906) met genome-wide significance (p=3.3 x 10-8), while two others on chr 6 (rs149447933) and chr 5 (rs541284506) were borderline (p=7.5 x 10-8 and p=9.5 x 10-8, respectively). The chr 22 SNP lies in the gene CELSR1, which is a cadherin and appears to be expressed in cardiac and smooth muscle. Conclusions: Our data suggest that Race and genetics impact HR in HFrEF patients, and identify a novel genetic locus influencing HR in CELSR1. Additional study is needed to better understand the relationship of race and genetics on HR as a treatment target in HFrEF.