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

TitleGenome-wide association study of heart rate and its variability in Hispanic/Latino cohorts.
Publication TypePublication
Year2017
AuthorsKerr KF, Avery CL, Lin HJ, Raffield LM, Zhang QS, Browning BL, Browning SR, Conomos MP, Gogarten SM, Laurie CC, Sofer T, Thornton TA, Hohensee C, Jackson RD, Kooperberg C, Li Y, Méndez-Giráldez R, Perez MV, Peters U, Reiner AP, Zhang Z-M, Yao J, Sotoodehnia N, Taylor KD, Guo X, Lange LA, Soliman EZ, Wilson JG, Rotter JI, Heckbert SR, Jain D, Whitsel EA
JournalHeart Rhythm
Volume14
Issue11
Pagination1675-1684
Date Published2017 11
ISSN1556-3871
KeywordsAfrican Americans, Arrhythmias, Cardiac, Autonomic Nervous System, Electrocardiography, genome-wide association study, Genotype, heart rate, Hispanic Americans, Humans, Phenotype, Polymorphism, Single Nucleotide, United States
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) or suggestive (P <10) 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.

DOI10.1016/j.hrthm.2017.06.018
Alternate JournalHeart Rhythm
PubMed ID28610988
PubMed Central IDPMC5671896
Grant ListN01 HC065234 / HC / NHLBI NIH HHS / United States
R01 CA059045 / CA / NCI NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
P01 HL060030 / HL / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
R01 HG006292 / HG / NHGRI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
N01 HC095167 / HC / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
R01 ES017794 / ES / NIEHS NIH HHS / United States
N01WH74316 / WH / WHI NIH HHS / United States
P01 GM099568 / GM / NIGMS NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
N01 HC095161 / HC / NHLBI NIH HHS / United States
R01 HL129132 / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
U01 CA137088 / CA / NCI NIH HHS / United States
N01 HC095164 / HC / NHLBI NIH HHS / United States
HHSN268201300048C / HL / NHLBI NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
N01 HC095166 / HC / NHLBI NIH HHS / United States
N01 HC065237 / HC / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01 HC095160 / HC / NHLBI NIH HHS / United States
N02HL64278 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01 HC065233 / HC / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
T32 HL129982 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
HHSN268201300049C / HL / NHLBI NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01 HC065236 / HC / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
N01 HC095169 / HC / NHLBI NIH HHS / United States
HHSN268201300047C / HL / NHLBI NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
HHSN268201300050C / HL / NHLBI NIH HHS / United States
N01 HC095165 / HC / NHLBI NIH HHS / United States
R21 HL121348 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
N01 HC065235 / HC / NHLBI NIH HHS / United States
N01 HC095168 / HC / NHLBI NIH HHS / United States
S10 OD020069 / OD / NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
HHSN268201300046C / HL / NHLBI NIH HHS / United States
T32 GM007266 / GM / NIGMS NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
N01 HC095163 / HC / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
N01 HC095162 / HC / NHLBI NIH HHS / United States
U01 HG005152 / HG / NHGRI NIH HHS / United States
P2C HD050924 / HD / NICHD NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
R01 HL127659 / HL / NHLBI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
R01 HL111089 / HL / NHLBI NIH HHS / United States
R01 HL116747 / HL / NHLBI NIH HHS / United States
N01 HC095159 / HC / NHLBI NIH HHS / United States
MS#: 
0320
Manuscript Lead/Corresponding Author Affiliation: 
HCHS/SOL Genetic Analysis Center - University of Washington, Seattle
ECI: 
Manuscript Status: 
Published