title: SCN5A variation is associated with electrocardiographic traits in the Jackson Heart Study.
abstract: BACKGROUND
  Understanding variation in the normal electric activity of the heart, assessed by the ECG, may provide a starting point for studies of susceptibility to serious arrhythmias such as sudden cardiac death during myocardial infarction or drug therapy. Recent genetic association studies of one ECG trait, the QT interval, have identified common variation in European-descent populations, but little is known about the genetic determinants of ECG traits in populations of African descent.
  
  
  RESULTS
  To identify genetic risk factors, we have undertaken a candidate gene study of ECG traits in collaboration with the Jackson Heart Study, a longitudinal study of 5301 blacks ascertained from the Jackson, Mississippi, area. Nine quantitative ECG traits were evaluated: P, PR, QRS, QT, and QTc durations, heart rate, and P, QRS, and T axes. We genotyped 72 variations in the predominant sodium channel gene expressed in heart, SCN5A, encoding the Na(v)1.5 voltage-gated sodium channel in 4558 subjects. Both rare and common variants in this gene have previously been associated with inherited arrhythmia syndromes and variable conduction. Adjusting for age, sex, and European ancestry, we performed tests of association in 3054 unrelated participants and identified 14 significant associations (P<1.0×10(-4)), of which 13 are independent, based on linkage disequilibrium. These variants explain up to 2% of the variation in ECG traits in the Jackson Heart Study.
  
  
  CONCLUSIONS
  These results suggest that SCN5A variation contributes to ECG trait distributions in blacks, and these same variations may be risk or protective factors associated with susceptibility to arrhythmias.
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232-0700, USA.
authors.forename: Janina M
authors.initials: JM
authors.lastname: Jeff
authors.forename: Kristin
authors.initials: K
authors.lastname: Brown-Gentry
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Buxbaum
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Sarpong
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.forename: Alfred L
authors.initials: AL
authors.lastname: George
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D062554:NAV1.5 Voltage-Gated Sodium Channel; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels