Several common variants modulate heart rate, PR interval and QRS duration

• Published in: Nature genetics Vol. 42; no. 2; pp. 117 - 122
• Main Authors: Holm, Hilma, Gudbjartsson, Daniel F, Arnar, David O, Thorleifsson, Gudmar, Thorgeirsson, Gudmundur, Stefansdottir, Hrafnhildur, Gudjonsson, Sigurjon A, Jonasdottir, Aslaug, Mathiesen, Ellisiv B, Njølstad, Inger, Nyrnes, Audhild, Wilsgaard, Tom, Hald, Erin M, Hveem, Kristian, Stoltenberg, Camilla, Løchen, Maja-Lisa, Kong, Augustine, Thorsteinsdottir, Unnur, Stefansson, Kari
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2010; Nature Publishing Group
• Subjects: 631/1647/2204/1453/1448; 631/208/205/2138; 631/208/727/2000; 692/699/75/29; Aged; Agriculture; Animal Genetics and Genomics; Arrhythmias, Cardiac - complications; Arrhythmias, Cardiac - genetics; Arrhythmias, Cardiac - physiopathology; Atrial fibrillation; Atrial Fibrillation - complications; Atrial Fibrillation - genetics; Atrial Fibrillation - physiopathology; Atrioventricular Block - complications; Atrioventricular Block - genetics; Atrioventricular Block - physiopathology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cardiac arrhythmia; Cardiac Myosins - genetics; Cardiovascular disease; Care and treatment; Data collection; Diagnosis; Electrocardiogram; Electrocardiography; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Function; Genetic aspects; Genetic Loci - genetics; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Health aspects; Heart attacks; Heart beat; Heart Conduction System - physiology; Heart rate; Heart Rate - genetics; Human Genetics; Humans; Iceland; Inheritance Patterns - genetics; Male; Measurement; Middle Aged; Mortality; Myosin Heavy Chains - genetics; Nitric oxide; Pacemaker, Artificial; Physiological aspects; Reproducibility of Results; Risk factors; Sick Sinus Syndrome - complications; Sick Sinus Syndrome - genetics; Sick Sinus Syndrome - physiopathology; Studies; Iceland; Norway; Heart rate; Variant
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.511

Hilma Holm and colleagues report genome-wide association studies to electrocardiographic measures of heart rate, PR interval, QRS duration and QT interval. 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 ∼10,000 individuals and followed up the top signals in an additional ∼10,000 individuals. We identified several genome-wide significant associations (with P < 1.6 × 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 × 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.