Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2
Year: 2017
Type: review
Study design: Observational Study
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: (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.
Source: Heart
Authors: Amanda A Seyerle, Henry J Lin, Stephanie M Gogarten, Adrienne Stilp, Raul Méndez Giráldez, Elsayed Soliman, Antoine Baldassari, Mariaelisa Graff, Susan Heckbert, Kathleen F Kerr, Charles Kooperberg, Carlos Rodriguez, Xiuqing Guo, Jie Yao, Nona Sotoodehnia, Kent D Taylor, Eric A Whitsel, Jerome I Rotter, Cathy C Laurie, Christy L Avery
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Health and Human Services, Office of Dietary Supplements, University of Miami, Northwestern University, San Diego State University, University of Washington, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Dental and Craniofacial Research, National Center for Research Resources, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
Awards: G1004541261, G1028935811, G1042216835, G1057152193, G1081972346, G1083745640, FHCRC High-Performance Computing Cluster, G1156594538, G1165142596, G1261793039, G1276754516, G1294553593, G1301356587, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-FIELD CENTER, G1312369436, G1409423729, Hispanic Community Health Study, G1446319095, G1455175283, G1462415530, G1483344193, G1497137905, G1508998135, G1516086731, G1522144118, G1558725192, G1587824183, G1640378483, G1666450717, G1686417863, G1740741465, G1828190173, G1888983140, G1917633662, G1922428914, G1983464145, G2031372691, SUBCLINICAL CARDIOVASCULAR DISEASE COORDINATING CENTER, G2095942735, G2128161193, G2135211244, G2135293100, G2144938473, G2161231279, G22458031, G2262782284, Genomics of Cardiac Electrical Activity and Arrhythmia, G2466919156, Institute for Clinical and Translational Research (UL1), HISPANIC COMMUNITY HEALTH STUDY - FIELD CENTER, G2501967490, G2528054427, G2545476352, G2575730562, G2636451769, G264148209, G2644289446, G2726417417, G2779429302, G2837638605, G283874107, G2878178050, G290884426, G291913881, G296458788, G2970637568, G297113894, G3062787641, G3093995152, G3106377335, G3161396180, G3252259982, G3255761503, UCLA Clinical and Translational Science Institute, Hispanic Community Health Study, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G3545534745, G3595232572, G3647016462, G3677686024, G3687594596, G3692229207, G36937976, G3796112702, G3838006641, G3852491038, G3919367648, G3952816605, G3990748671, G399481048, G4021838900, G4036023366, Genomics of Sudden Cardiac Arrest Among African Americans, G4121762840, G4165985951, G4186273061, G4240450635, G4309390892, G4312823968, G433713863, Hispanic Community Health Study, G4430667546, G4438318499, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, G4512137732, G4552920371, G4588218921, G4752697780, G4860668542, G4940192625, G4986157935, G4989378220, G5075046117, G51047235, G5108002584, G5129651400, G5223154479, G528357465, G5365244667, G5397198720, G543802643, G5547620395, G555858244, G5605591545, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G5624510383, G5653954166, G5654179670, G569253488, G5705373727, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G5739677117, G5787256936, G5878028785, G5906656038, G5993399974, G6045475270, G6075306088, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY, G6095866717, G611940047, G614814196, G6156511736, G619791618, G6359107525, Institute for Clinical and Translational Research, G6514094751, G6585687856, G66341962, G6744188800, G6856766826, G6868531854, G6967911674, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY, G7057037114, G713258703, G7166352866, G7203655167, G7239480477, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G7272721675, G7278742613, G729036485, G7408420985, G7513901258, G7678550560, G78770644, G7924587209, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, Clinical and Translational Science Award, G8102260223, G8145863542, G818308888, G820454163, G8386326007, G8472503103, G8536616440, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-FIELD CENTER, HISPANIC COMMUNITY HEALTH STUDY-268065233, G8840902395, G8852914737, G8904081916, G8938298865, G9000004549, G9000004784, G9000006353, G9000017360, G9000019818, G9000025517, G9000063950, G9000065698, G9000140433, Diabetes Research Center (DRC), Cardiovascular Epidemiology Training Grant, G991334795
OpenAlex ID: W2767207873