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

Ilkhanoff, Leonard; Arking, Dan E.; Lemaitre, Rozenn N.; Alonso, Alvaro; Chen, Lin Y.; Durda, Peter; Hesselson, Stephanie E.; Kerr, Kathleen F.; Magnani, Jared W. and Marcus, Gregory M., et al. (2014) In Journal of Cardiovascular Electrophysiology 25(11). p.1150-1157
Abstract
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],... (More)
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. (Less)
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published
subject
keywords
atrial fibrillation, electrocardiogram, genetics, PR interval, sudden, death
in
Journal of Cardiovascular Electrophysiology
volume
25
issue
11
pages
1150 - 1157
publisher
Wiley-Blackwell
external identifiers
  • wos:000344470300002
  • scopus:84911932961
ISSN
1540-8167
DOI
10.1111/jce.12483
language
English
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yes
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c540f12f-4ac0-4046-bea4-10096d97b754 (old id 4865309)
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2015-01-07 10:32:29
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2017-09-03 03:20:09
@article{c540f12f-4ac0-4046-bea4-10096d97b754,
  abstract     = {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.},
  author       = {Ilkhanoff, Leonard and Arking, Dan E. and Lemaitre, Rozenn N. and Alonso, Alvaro and Chen, Lin Y. and Durda, Peter and Hesselson, Stephanie E. and Kerr, Kathleen F. and Magnani, Jared W. and Marcus, Gregory M. and Schnabel, Renate B. and Smith, Gustav and Soliman, Elsayed Z. and Reiner, Alexander P. and Sotoodehnia, Nona},
  issn         = {1540-8167},
  keyword      = {atrial fibrillation,electrocardiogram,genetics,PR interval,sudden,death},
  language     = {eng},
  number       = {11},
  pages        = {1150--1157},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Cardiovascular Electrophysiology},
  title        = {A Common SCN5A Variant Is Associated with PR Interval and Atrial Fibrillation Among African Americans},
  url          = {http://dx.doi.org/10.1111/jce.12483},
  volume       = {25},
  year         = {2014},
}