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Gustav Smith

Associate professor

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A Common SCN5A Variant Is Associated with PR Interval and Atrial Fibrillation Among African Americans

Author

  • 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
  • Gustav Smith
  • Elsayed Z. Soliman
  • Alexander P. Reiner
  • Nona Sotoodehnia

Summary, in English

rs7629265 and AF Risk ObjectiveWe examined the association of rs7626962 (S1103Y) or rs7629265, a variant in high linkage disequilibrium with S1103Y (r(2) = 0.87 - 1), with sudden cardiac death (SCD) and atrial fibrillation (AF) among African Americans. BackgroundThe 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. MethodsUsing 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). ResultsMeta-analyses across 5 cohorts demonstrated that rs7629265 was significantly associated with PR duration ( = -4.1 milliseconds; P = 2.2x10(-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 x 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). ConclusionThe 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.

Department/s

  • Cardiology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2014

Language

English

Pages

1150-1157

Publication/Series

Journal of Cardiovascular Electrophysiology

Volume

25

Issue

11

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Cardiac and Cardiovascular Systems

Keywords

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

Status

Published

ISBN/ISSN/Other

  • ISSN: 1540-8167