Genome-Wide Association Study of Heart Rate and Its Variability in Hispanic/Latino Cohorts

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Citation

Kerr, Kathleen F.; Avery, Christy L.; Lin, Henry J.; Raffield, Laura M.; Zhang, Qian S.; Browning, Brian L.; Browning, Sharon R.; Conomos, Matthew P.; Gogarten, Stephanie M.; & Laurie, Cathy C., et al. (2017). Genome-Wide Association Study of Heart Rate and Its Variability in Hispanic/Latino Cohorts. Heart Rhythm, 14(11), 1675-1684. PMCID: PMC5671896

Abstract

BACKGROUND: Although time-domain measures of heart rate variability (HRV) are used to estimate cardiac autonomic tone and disease risk in multi-ethnic populations, the genetic epidemiology of HRV in Hispanics/Latinos has not been characterized.
OBJECTIVE: Conduct a genome-wide association study (GWAS) 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 (beats/min), the standard deviation of normal-to-normal inter-beat intervals (SDNN, ms), and the root mean squared difference in successive, normal-to-normal inter-beat intervals (RMSSD, ms) from resting, standard twelve-lead electrocardiograms. 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<5x10-8) or suggestive (P<10-6) significance thresholds.
RESULTS: Two genome-wide significant SNPs replicated in a European ancestry cohort, 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.
CONCLUSIONS: This first GWAS 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.

URL

http://dx.doi.org/10.1016/j.hrthm.2017.06.018

Reference Type

Journal Article

Year Published

2017

Journal Title

Heart Rhythm

Author(s)

Kerr, Kathleen F.
Avery, Christy L.
Lin, Henry J.
Raffield, Laura M.
Zhang, Qian S.
Browning, Brian L.
Browning, Sharon R.
Conomos, Matthew P.
Gogarten, Stephanie M.
Laurie, Cathy C.
Sofer, Tamar
Thornton, Timothy A.
Hohensee, Chancellor
Jackson, Rebecca D.
Kooperberg, Charles L.
Li, Yun
Mendez-Giraldez, Raul
Perez, Marco V.
Peters, Ulrike
Reiner, Alexander P.
Zhang, Zhu-Ming
Yao, Jie
Sotoodehnia, Nona
Taylor, Kent D.
Guo, Xiuqing
Lange, Leslie A.
Soliman, Elsayed Z.
Wilson, James G.
Rotter, Jerome I.
Heckbert, Susan R.
Jain, Deepti
Whitsel, Eric A.

PMCID

PMC5671896

ORCiD

Avery - 0000-0002-1044-8162