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Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.

TitleNovel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.
Publication TypeJournal Article
Year of Publication2012
AuthorsButler, AM, Yin, X, Evans, DS, Nalls, MA, Smith, EN, Tanaka, T, Li, G, Buxbaum, SG, Whitsel, EA, Alonso, A, Arking, DE, Benjamin, EJ, Berenson, GS, Bis, JC, Chen, W, Deo, R, Ellinor, PT, Heckbert, SR, Heiss, G, Hsueh, W-C, Keating, BJ, Kerr, KF, Li, Y, Limacher, MC, Liu, Y, Lubitz, SA, Marciante, KD, Mehra, R, Meng, YA, Newman, AB, Newton-Cheh, C, North, KE, Palmer, CD, Psaty, BM, P Quibrera, M, Redline, S, Reiner, AP, Rotter, JI, Schnabel, RB, Schork, NJ, Singleton, AB, J Smith, G, Soliman, EZ, Srinivasan, SR, Zhang, Z-M, Zonderman, AB, Ferrucci, L, Murray, SS, Evans, MK, Sotoodehnia, N, Magnani, JW, Avery, CL
JournalCirc Cardiovasc Genet
Volume5
Issue6
Pagination639-46
Date Published2012 Dec
ISSN1942-3268
KeywordsAdult, African Americans, Cohort Studies, Electrocardiography, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide
Abstract<p><b>BACKGROUND: </b>The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans.</p><p><b>METHODS AND RESULTS: </b>We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0 × 10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0 × 10(-8)).</p><p><b>CONCLUSIONS: </b>This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.</p>
DOI10.1161/CIRCGENETICS.112.963991
Alternate JournalCirc Cardiovasc Genet
PubMed ID23139255
PubMed Central IDPMC3560365
Grant ListHC-85083 / HC / NHLBI NIH HHS / United States
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HHSN268201100012C / HL / NHLBI NIH HHS / United States
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