title: Several common variants modulate heart rate, PR interval and QRS duration.
abstract: 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.
authors.affiliation: deCODE genetics, Reykjavik, Iceland. hilma.holm@decode.is
authors.forename: Hilma
authors.initials: H
authors.lastname: Holm
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: David O
authors.initials: DO
authors.lastname: Arnar
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Thorgeirsson
authors.forename: Hrafnhildur
authors.initials: H
authors.lastname: Stefansdottir
authors.forename: Sigurjon A
authors.initials: SA
authors.lastname: Gudjonsson
authors.forename: Aslaug
authors.initials: A
authors.lastname: Jonasdottir
authors.forename: Ellisiv B
authors.initials: EB
authors.lastname: Mathiesen
authors.forename: Inger
authors.initials: I
authors.lastname: Njølstad
authors.forename: Audhild
authors.initials: A
authors.lastname: Nyrnes
authors.forename: Tom
authors.initials: T
authors.lastname: Wilsgaard
authors.forename: Erin M
authors.initials: EM
authors.lastname: Hald
authors.forename: Kristian
authors.initials: K
authors.lastname: Hveem
authors.forename: Camilla
authors.initials: C
authors.lastname: Stoltenberg
authors.forename: Maja-Lisa
authors.initials: ML
authors.lastname: Løchen
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: 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
chemical_list: C094239:MYH6 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains