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Heart Rhythm. 2017 Nov;14(11):1675-1684. doi: 10.1016/j.hrthm.2017.06.018. Epub 2017 Jun 10.

Genome-wide association study of heart rate and its variability in Hispanic/Latino cohorts.

Author information

1
Department of Biostatistics, University of Washington, Seattle, Washington. Electronic address: katiek@uw.edu.
2
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
3
The Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, California.
4
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
5
Department of Biostatistics, University of Washington, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
6
Department of Medicine, University of Washington, Seattle, Washington.
7
Department of Biostatistics, University of Washington, Seattle, Washington.
8
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
9
Division of Endocrinology, Diabetes and Metabolism, College of Medicine, The Ohio State University, Columbus, Ohio.
10
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
11
Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University, Palo Alto, California.
12
Department of Epidemiology, University of Washington, Seattle, Washington.
13
Epidemiological Cardiology Research Center (EPICARE), Wake Forest School of Medicine, Winston Salem, North Carolina.
14
Department of Epidemiology, University of Washington, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.
15
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
16
Department of Epidemiology, University of Washington, Seattle, Washington; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.
17
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Abstract

BACKGROUND:

Although time-domain measures of heart rate variability (HRV) are used to estimate cardiac autonomic tone and disease risk in multiethnic populations, the genetic epidemiology of HRV in Hispanics/Latinos has not been characterized.

OBJECTIVE:

The purpose of this study was to conduct a genome-wide association study of heart rate (HR) and its variability in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Women's Health Initiative Hispanic SNP-Health Association Resource project (n = 13,767).

METHODS:

We estimated HR (bpm), standard deviation of normal-to-normal interbeat intervals (SDNN, ms), and root mean squared difference in successive, normal-to-normal interbeat intervals (RMSSD, ms) from resting, standard 12-lead ECGs. We estimated associations between each phenotype and 17 million genotyped or imputed single nucleotide polymorphisms (SNPs), accounting for relatedness and adjusting for age, sex, study site, and ancestry. Cohort-specific estimates were combined using fixed-effects, inverse-variance meta-analysis. We investigated replication for select SNPs exceeding genome-wide (P <5 × 10-8) or suggestive (P <10-6) significance thresholds.

RESULTS:

Two genome-wide significant SNPs replicated in a European ancestry cohort, 1 one for RMSSD (rs4963772; chromosome 12) and another for SDNN (rs12982903; chromosome 19). A suggestive SNP for HR (rs236352; chromosome 6) replicated in an African-American cohort. Functional annotation of replicated SNPs in cardiac and neuronal tissues identified potentially causal variants and mechanisms.

CONCLUSION:

This first genome-wide association study of HRV and HR in Hispanics/Latinos underscores the potential for even modestly sized samples of non-European ancestry to inform the genetic epidemiology of complex traits.

KEYWORDS:

Autonomic nervous system; Electrocardiogram; Epidemiology; Genetic association studies; Ion channels/membrane transport

PMID:
28610988
PMCID:
PMC5671896
DOI:
10.1016/j.hrthm.2017.06.018
[Indexed for MEDLINE]
Free PMC Article

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