A common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans

Leonard Ilkhanoff, Dan E. Arking, Rozenn N. Lemaitre, Alvaro Alonso, Lin Y. Chen, Peter Durda, Stephanie E. Hesselson, Kathleen F. Kerr, Jared W. Magnani, Gregory M. Marcus, Renate B. Schnabel, J. Gustav Smith, Elsayed Z. Soliman, Alexander P. Reiner, Nona Sotoodehnia

Research output: Contribution to journalArticle

Abstract

rs7629265 and AF Risk Objective We examined the association of rs7626962 (S1103Y) or rs7629265, a variant in high linkage disequilibrium with S1103Y (r2 = 0.87 - 1), with sudden cardiac death (SCD) and atrial fibrillation (AF) among African Americans. Background The SCN5A missense variant S1103Y has been associated with SCD among African Americans in small case-control studies, but larger population-based studies are needed to validate these findings. The association of this variant with AF has not been fully explored.

Methods Using genotyping data on over 7,000 African Americans from 5 cohorts (Atherosclerosis Risk in Communities [ARIC], Cleveland Family Study [CFS], Jackson Heart Study [JHS], Multi-Ethnic Study of Atherosclerosis [MESA], Cardiovascular Health Study [CHS]), we examined the association of rs7629265 with electrocardiographic PR, QRS, and QT intervals, and with incident AF and SCD. We examined association of S1103Y (rs7626962) with SCD using a population-based case-control study of SCD Cardiac Arrest Blood Study (CABS).

Results Meta-analyses across 5 cohorts demonstrated that rs7629265 was significantly associated with PR duration (β = -4.1 milliseconds; P = 2.2×10-6), but not significantly associated with QRS or QT intervals. In meta-analyses of prospectively followed ARIC and CHS participants (n = 3,656), rs7629265 was associated with increased AF risk (n = 299 AF cases; HR = 1.74, P = 1.9 × 10-4). By contrast, rs7629265 was not significantly associated with SCD risk in ARIC (n = 83 SCD cases; P = 0.30) or CHS (n = 54 SCD cases; P = 0.47). Similarly, S1103Y was not significantly associated with SCD risk in CABS (n = 225 SCD cases; P = 0.29).

Conclusion The common SCN5A variant, rs7629265, is associated with increased AF risk and shorter PR interval among African Americans. In contrast to prior reports, we found no evidence of association of rs7629265 or rs7626962 (S1103Y) with SCD risk in the general population.

Original languageEnglish (US)
Pages (from-to)1150-1157
Number of pages8
JournalJournal of cardiovascular electrophysiology
Volume25
Issue number11
DOIs
StatePublished - Nov 1 2014

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Keywords

  • PR interval
  • atrial fibrillation
  • electrocardiogram
  • genetics
  • sudden death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Ilkhanoff, L., Arking, D. E., Lemaitre, R. N., Alonso, A., Chen, L. Y., Durda, P., Hesselson, S. E., Kerr, K. F., Magnani, J. W., Marcus, G. M., Schnabel, R. B., Smith, J. G., Soliman, E. Z., Reiner, A. P., & Sotoodehnia, N. (2014). A common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans. Journal of cardiovascular electrophysiology, 25(11), 1150-1157. https://doi.org/10.1111/jce.12483