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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
Secondary AuthorsAvery 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

BACKGROUND: 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.

METHODS AND RESULTS: 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

CONCLUSIONS: 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.

DOI10.1161/CIRCGENETICS.112.963991
Alternate JournalCirc Cardiovasc Genet
PubMed ID23139255
PubMed Central IDPMC3560365
Grant ListHC-85083 / HC / NHLBI NIH HHS / United States
M01-RR00425 / RR / NCRR NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
ZIA AG000513-11 / / Intramural NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
N01 WH032112 / WH / WHI NIH HHS / United States
N01 WH042122 / WH / WHI NIH HHS / United States
R00 HL098458 / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
CA009330 / CA / NCI NIH HHS / United States
HC-85082 / HC / NHLBI NIH HHS / United States
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HG006703 / HG / NHGRI NIH HHS / United States
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