Genome-wide analyses identify SCN5A as a susceptibility locus for premature atrial contraction frequency
Sébastien Thériault,
Medea Imboden,
Mary L. Biggs,
Thomas R. Austin,
Stefanie Aeschbacher,
Emmanuel Schaffner,
Jennifer A. Brody,
Traci M. Bartz,
Martin Risch,
Kirsten Grossmann,
Henry J. Lin,
Elsayed Z. Soliman,
Wendy S. Post,
Lorenz Risch,
Jose E. Krieger,
Alexandre C. Pereira,
Susan R. Heckbert,
Nona Sotoodehnia,
Nicole M. Probst-Hensch,
David Conen
Affiliations
Sébastien Thériault
Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec City, QC, Canada; Population Health Research Institute, McMaster University, Hamilton, ON, Canada; Corresponding author
Medea Imboden
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland
Mary L. Biggs
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Department of Biostatistics, University of Washington, Seattle, WA, USA
Thomas R. Austin
Department of Epidemiology, University of Washington, Seattle, WA, USA
Stefanie Aeschbacher
Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland; Department of Cardiology, University Hospital of Basel, Basel, Switzerland
Emmanuel Schaffner
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland
Jennifer A. Brody
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
Traci M. Bartz
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Department of Biostatistics, University of Washington, Seattle, WA, USA
Martin Risch
Dr. Risch Medical Laboratories, Vaduz, Liechtenstein; Division of Laboratory Medicine, Cantonal Hospital Graubünden, Chur, Switzerland
Kirsten Grossmann
Dr. Risch Medical Laboratories, Vaduz, Liechtenstein; Faculty of Medical Sciences, Private University in the Principality of Liechtenstein, Triesen, Liechtenstein
Henry J. Lin
Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
Elsayed Z. Soliman
Epidemiological Cardiology Research Center, Section on Cardiovascular Medicine, Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
Wendy S. Post
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Lorenz Risch
Dr. Risch Medical Laboratories, Vaduz, Liechtenstein; Center of Laboratory Medicine, University Institute of Clinical Chemistry, University of Bern, Bern, Switzerland
Jose E. Krieger
Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of Sao Paulo Medical School, Sao Paulo, Brazil
Alexandre C. Pereira
Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of Sao Paulo Medical School, Sao Paulo, Brazil
Susan R. Heckbert
Department of Epidemiology, University of Washington, Seattle, WA, USA; Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA
Nona Sotoodehnia
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Cardiology Division, University of Washington, Seattle, WA, USA
Nicole M. Probst-Hensch
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland
David Conen
Population Health Research Institute, McMaster University, Hamilton, ON, Canada
Summary: Premature atrial contractions (PACs) are frequently observed on electrocardiograms and are associated with increased risks of atrial fibrillation (AF), stroke, and mortality. In this study, we aimed to identify genetic susceptibility loci for PAC frequency. We performed a genome-wide association study meta-analysis with PAC frequency obtained from ambulatory cardiac monitoring in 4,831 individuals of European ancestry. We identified a genome-wide significant locus at the SCN5A gene. The lead variant, rs7373862, located in an intron of SCN5A, was associated with an increase of 0.12 [95% CI 0.08–0.16] standard deviations of the normalized PAC frequency per risk allele. Among genetic variants previously associated with AF, there was a significant enrichment in concordance of effect for PAC frequency (n = 73/106, p = 5.1 × 10−5). However, several AF risk loci, including PITX2, were not associated with PAC frequency. These findings suggest the existence of both shared and distinct genetic mechanisms for PAC frequency and AF.
