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Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at .

TitleGenome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at .
Publication TypePublication
Year2018
AuthorsSeyerle AA, Lin HJ, Gogarten SM, Stilp A, Giráldez RMéndez, Soliman E, Baldassari A, Graff M, Heckbert S, Kerr KF, Kooperberg C, Rodriguez C, Guo X, Yao J, Sotoodehnia N, Taylor KD, Whitsel EA, Rotter JI, Laurie CC, Avery CL
JournalHeart
Volume104
Issue11
Pagination904-911
Date Published2018 06
ISSN1468-201X
KeywordsAtrial Fibrillation, Atrioventricular Node, Electrocardiography, Female, genome-wide association study, Genotype, Hispanic Americans, Humans, Inhibitor of Differentiation Protein 2, Male, Middle Aged, Polymorphism, Single Nucleotide
Abstract

OBJECTIVE: PR interval (PR) is a heritable electrocardiographic measure of atrial and atrioventricular nodal conduction. Changes in PR duration may be associated with atrial fibrillation, heart failure and all-cause mortality. Hispanic/Latino populations have high burdens of cardiovascular morbidity and mortality, are highly admixed and represent exceptional opportunities for novel locus identification. However, they remain chronically understudied. We present the first genome-wide association study (GWAS) of PR in 14 756 participants of Hispanic/Latino ancestry from three studies.METHODS: Study-specific summary results of the association between 1000 Genomes Phase 1 imputed single-nucleotide polymorphisms (SNPs) and PR assumed an additive genetic model and were adjusted for global ancestry, study centre/region and clinical covariates. Results were combined using fixed-effects, inverse variance weighted meta-analysis. Sequential conditional analyses were used to identify independent signals. Replication of novel loci was performed in populations of Asian, African and European descent. ENCODE and RoadMap data were used to annotate results.RESULTS: We identified a novel genome-wide association (P<5×10) with PR at (rs6730558), which replicated in Asian and European populations (P<0.017). Additionally, we generalised 10 previously identified PR loci to Hispanics/Latinos. Bioinformatics annotation provided evidence for regulatory function in cardiac tissue. Further, for six loci that generalised, the Hispanic/Latino index SNP was genome-wide significant and identical to (or in high linkage disequilibrium with) the previously identified GWAS lead SNP.CONCLUSIONS: Our results suggest that genetic determinants of PR are consistent across race/ethnicity, but extending studies to admixed populations can identify novel associations, underscoring the importance of conducting genetic studies in diverse populations.

DOI10.1136/heartjnl-2017-312045
Alternate JournalHeart
PubMed ID29127183
PubMed Central IDPMC6946379
Grant ListN01HC95160 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
N01 HC095165 / HC / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
N01 HC095168 / HC / NHLBI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
N01 HC095159 / HC / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
HHSN268201000031C / HL / NHLBI NIH HHS / United States
N01 HC095167 / HC / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
HHSN268201500001C / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
N01 HC095161 / HC / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01 HC095164 / HC / 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
N01HC95164 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01 HC095160 / HC / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
T32 HL007779 / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
N01HC65237 / 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
HHSN268201500001I / HL / 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
S10 OD020069 / OD / NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
N01 HC095162 / HC / NHLBI NIH HHS / United States
T32 HL007055 / 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
MS#: 
0310
Manuscript Lead/Corresponding Author Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
ECI: 
Yes
Manuscript Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
Manuscript Status: 
Published