title: A common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans.
abstract: OBJECTIVE
  We 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine, Division of Cardiology, Section of Electrophysiology, Northwestern University, Chicago, Illinois, USA.
authors: Leonard
authors: L
authors: Ilkhanoff
authors: Dan E
authors: DE
authors: Arking
authors: Rozenn N
authors: RN
authors: Lemaitre
authors: Alvaro
authors: A
authors: Alonso
authors: Lin Y
authors: LY
authors: Chen
authors: Peter
authors: P
authors: Durda
authors: Stephanie E
authors: SE
authors: Hesselson
authors: Kathleen F
authors: KF
authors: Kerr
authors: Jared W
authors: JW
authors: Magnani
authors: Gregory M
authors: GM
authors: Marcus
authors: Renate B
authors: RB
authors: Schnabel
authors: J Gustav
authors: JG
authors: Smith
authors: Elsayed Z
authors: EZ
authors: Soliman
authors: Alexander P
authors: AP
authors: Reiner
authors: Nona
authors: N
authors: Sotoodehnia
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D015331:Cohort Studies; D016757:Death, Sudden, Cardiac; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D016037:Single-Blind Method
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
keywords: PR interval; atrial fibrillation; electrocardiogram; genetics; sudden death