Mitochondrial DNA copy number and incident atrial fibrillation

Authors

Di Zhao, Welch Center for Prevention Epidemiology and Clinical Research
Traci M. Bartz, University of Washington
Nona Sotoodehnia, University of Washington
Wendy S. Post, Welch Center for Prevention Epidemiology and Clinical Research
Susan R. Heckbert, University of Washington
Alvaro Alonso, Rollins School of Public Health
Ryan J. Longchamps, Johns Hopkins School of Medicine
Christina A. Castellani, Johns Hopkins School of MedicineFollow
Yun Soo Hong, Welch Center for Prevention Epidemiology and Clinical Research
Jerome I. Rotter, Harbor-UCLA Medical Center
Henry J. Lin, Harbor-UCLA Medical Center
Brian O'Rourke, Johns Hopkins School of Medicine
Nathan Pankratz, University of Minnesota Twin Cities
John A. Lane, University of Minnesota Twin Cities
Stephanie Y. Yang, Johns Hopkins School of Medicine
Eliseo Guallar, Welch Center for Prevention Epidemiology and Clinical Research
Dan E. Arking, Johns Hopkins School of Medicine

Document Type

Article

Publication Date

9-16-2020

Journal

BMC Medicine

Volume

18

Issue

1

URL with Digital Object Identifier

10.1186/s12916-020-01715-6

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.