Several common variants modulate heart rate, PR interval and QRS duration.
Electrocardiographic measures are indicative of the function of the cardiac conduction system. To search for sequence variants that modulate heart rate, PR interval and QRS duration in individuals of European descent, we performed a genome-wide association study in approximately 10,000 individuals and followed up the top signals in an additional approximately 10,000 individuals. We identified several genome-wide significant associations (with P < 1.6 x 10(-7)). We identified one locus for heart rate (MYH6), four for PR interval (TBX5, SCN10A, CAV1 and ARHGAP24) and four for QRS duration (TBX5, SCN10A, 6p21 and 10q21). We tested for association between these loci and subjects with selected arrhythmias in Icelandic and Norwegian case-control sample sets. We observed correlations between TBX5 and CAV1 and atrial fibrillation (P = 4.0 x 10(-5) and P = 0.00032, respectively), between TBX5 and advanced atrioventricular block (P = 0.0067), and between SCN10A and pacemaker implantation (P = 0.0029). We also replicated previously described associations with the QT interval.
Holm
Hilma
H
deCODE genetics, Reykjavik, Iceland. hilma.holm@decode.is
Gudbjartsson
Daniel F
DF
Arnar
David O
DO
Thorleifsson
Gudmar
G
Thorgeirsson
Gudmundur
G
Stefansdottir
Hrafnhildur
H
Gudjonsson
Sigurjon A
SA
Jonasdottir
Aslaug
A
Mathiesen
Ellisiv B
EB
Njølstad
Inger
I
Nyrnes
Audhild
A
Wilsgaard
Tom
T
Hald
Erin M
EM
Hveem
Kristian
K
Stoltenberg
Camilla
C
Løchen
Maja-Lisa
ML
Kong
Augustine
A
Thorsteinsdottir
Unnur
U
Stefansson
Kari
K
D000368:Aged; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D054537:Atrioventricular Block / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D024722:Cardiac Myosins / Q000235:genetics; D004562:Electrocardiography; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006329:Heart Conduction System / Q000502:physiology*; D006339:Heart Rate / Q000235:genetics*; D006801:Humans; D007055:Iceland; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018995:Myosin Heavy Chains / Q000235:genetics; D010138:Pacemaker, Artificial; D015203:Reproducibility of Results; D012804:Sick Sinus Syndrome / Q000150:complications / Q000235:genetics / Q000503:physiopathology
C094239:MYH6 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains