Title | Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at . |
Publication Type | Publication |
Year | 2018 |
Authors | Seyerle 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 |
Journal | Heart |
Volume | 104 |
Issue | 11 |
Pagination | 904-911 |
Date Published | 2018 Jun |
ISSN | 1468-201X |
Keywords | Atrial Fibrillation, Atrioventricular Node, Electrocardiography, Female, genome-wide association study, Genotype, Hispanic or Latino, 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. |
DOI | 10.1136/heartjnl-2017-312045 |
Alternate Journal | Heart |
PubMed ID | 29127183 |
PubMed Central ID | PMC6946379 |
Grant List | N01HC95160 / HL / NHLBI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States N01HC95168 / HL / 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 N01 HC095165 / HC / NHLBI NIH HHS / United States HHSN268201500003I / HL / NHLBI NIH HHS / United States S10 OD020069 / OD / NIH HHS / United States UL1 TR000040 / TR / NCATS NIH HHS / United States HHSN268201100003I / HL / NHLBI 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 |
Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at .
MS#:
0310
ECI:
Yes
Manuscript Affiliation:
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
Manuscript Status:
Published