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

Publication ,  Journal Article
Butler, AM; Yin, X; Evans, DS; Nalls, MA; Smith, EN; Tanaka, T; Li, G; Buxbaum, SG; Whitsel, EA; Alonso, A; Arking, DE; Benjamin, EJ; Bis, JC ...
Published in: Circ Cardiovasc Genet
December 2012

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<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)). 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.

Duke Scholars

Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

December 2012

Volume

5

Issue

6

Start / End Page

639 / 646

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Loci
  • Female
  • Electrocardiography
  • Cohort Studies
 

Citation

APA
Chicago
ICMJE
MLA
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Butler, A. M., Yin, X., Evans, D. S., Nalls, M. A., Smith, E. N., Tanaka, T., … Avery, C. L. (2012). Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts. Circ Cardiovasc Genet, 5(6), 639–646. https://doi.org/10.1161/CIRCGENETICS.112.963991
Butler, Anne M., Xiaoyan Yin, Daniel S. Evans, Michael A. Nalls, Erin N. Smith, Toshiko Tanaka, Guo Li, et al. “Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.Circ Cardiovasc Genet 5, no. 6 (December 2012): 639–46. https://doi.org/10.1161/CIRCGENETICS.112.963991.
Butler AM, Yin X, Evans DS, Nalls MA, Smith EN, Tanaka T, et al. Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts. Circ Cardiovasc Genet. 2012 Dec;5(6):639–46.
Butler, Anne M., et al. “Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.Circ Cardiovasc Genet, vol. 5, no. 6, Dec. 2012, pp. 639–46. Pubmed, doi:10.1161/CIRCGENETICS.112.963991.
Butler 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, Quibrera PM, Redline S, Reiner AP, Rotter JI, Schnabel RB, Schork NJ, Singleton AB, Smith JG, Soliman EZ, Srinivasan SR, Zhang Z-M, Zonderman AB, Ferrucci L, Murray SS, Evans MK, Sotoodehnia N, Magnani JW, Avery CL. Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts. Circ Cardiovasc Genet. 2012 Dec;5(6):639–646.

Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

December 2012

Volume

5

Issue

6

Start / End Page

639 / 646

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Loci
  • Female
  • Electrocardiography
  • Cohort Studies