Mitochondrial DNA copy number and incident atrial fibrillation
Di Zhao,
Traci M. Bartz,
Nona Sotoodehnia,
Wendy S. Post,
Susan R. Heckbert,
Alvaro Alonso,
Ryan J. Longchamps,
Christina A. Castellani,
Yun Soo Hong,
Jerome I. Rotter,
Henry J. Lin,
Brian O’Rourke,
Nathan Pankratz,
John A. Lane,
Stephanie Y. Yang,
Eliseo Guallar,
Dan E. Arking
Affiliations
Di Zhao
Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health
Traci M. Bartz
Departments of Biostatistics and Medicine, University of Washington
Nona Sotoodehnia
Departments of Biostatistics and Medicine, University of Washington
Wendy S. Post
Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health
Susan R. Heckbert
Department of Epidemiology, University of Washington School of Public Health
Alvaro Alonso
Department of Epidemiology, Rollins School of Public Health, Emory University
Ryan J. Longchamps
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
Christina A. Castellani
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
Yun Soo Hong
Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health
Jerome I. Rotter
Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Henry J. Lin
Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Brian O’Rourke
Department of Medicine, Johns Hopkins University School of Medicine
Nathan Pankratz
Department of Laboratory Medicine and Pathology, University of Minnesota
John A. Lane
Department of Laboratory Medicine and Pathology, University of Minnesota
Stephanie Y. Yang
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
Eliseo Guallar
Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health
Dan E. Arking
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
Abstract Background Mechanistic studies suggest that mitochondria DNA (mtDNA) dysfunction may be associated with increased risk of atrial fibrillation (AF). The association between mtDNA copy number (mtDNA-CN) and incident AF in the general population, however, remains unknown. Methods We conducted prospective analyses of 19,709 participants from the Atherosclerosis Risk in Communities Study (ARIC), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Cardiovascular Health Study (CHS). mtDNA-CN from the peripheral blood was calculated from probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms (SNP) Array 6.0 in ARIC and MESA and from multiplexed real-time quantitative polymerase chain reaction (qPCR) in CHS. Incident AF cases were identified through electrocardiograms, review of hospital discharge codes, Medicare claims, and death certificates. Results The median follow-up time was 21.4 years in ARIC, 12.9 years in MESA, and 11.0 years in CHS, during which 4021 participants developed incident atrial fibrillation (1761 in ARIC, 790 in MESA, and 1470 in CHS). In fully adjusted models, participants with the lowest quintile of mitochondria DNA copy number had an overall 13% increased risk (95% CI 1 to 27%) of incident atrial fibrillation compared to those with the highest quintile. Dose-response spline analysis also showed an inverse association between mitochondria DNA copy number and hazard for atrial fibrillation for all three cohorts. These associations were consistent across subgroups. Conclusions Mitochondria DNA copy number was inversely associated with the risk of AF independent of traditional cardiovascular risk factors. These findings implicate mitochondria DNA copy number as a novel risk factor for atrial fibrillation. Further research is warranted to understand the underlying mechanisms and to evaluate the role of mitochondria DNA copy number in the management of atrial fibrillation risk.
