Mitochondrial DNA copy number and incident atrial fibrillation
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | BMC Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12916-020-01715-6 |
| _version_ | 1818047327632359424 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Di Zhao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T10:03:57Z |
| format | Article |
| id | doaj.art-252c2d273dba4941b72da4413ca8d99a |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-12-10T10:03:57Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-252c2d273dba4941b72da4413ca8d99a2022-12-22T01:53:17ZengBMCBMC Medicine1741-70152020-09-0118111110.1186/s12916-020-01715-6Mitochondrial DNA copy number and incident atrial fibrillationDi Zhao0Traci M. Bartz1Nona Sotoodehnia2Wendy S. Post3Susan R. Heckbert4Alvaro Alonso5Ryan J. Longchamps6Christina A. Castellani7Yun Soo Hong8Jerome I. Rotter9Henry J. Lin10Brian O’Rourke11Nathan Pankratz12John A. Lane13Stephanie Y. Yang14Eliseo Guallar15Dan E. Arking16Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public HealthDepartments of Biostatistics and Medicine, University of WashingtonDepartments of Biostatistics and Medicine, University of WashingtonDepartments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public HealthDepartment of Epidemiology, University of Washington School of Public HealthDepartment of Epidemiology, Rollins School of Public Health, Emory UniversityMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of MedicineMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of MedicineDepartments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public HealthInstitute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical CenterInstitute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical CenterDepartment of Medicine, Johns Hopkins University School of MedicineDepartment of Laboratory Medicine and Pathology, University of MinnesotaDepartment of Laboratory Medicine and Pathology, University of MinnesotaMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of MedicineDepartments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public HealthMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s12916-020-01715-6Mitochondria DNA copy numbermtDNAAtrial fibrillation |
| spellingShingle | 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 Mitochondrial DNA copy number and incident atrial fibrillation BMC Medicine Mitochondria DNA copy number mtDNA Atrial fibrillation |
| title | Mitochondrial DNA copy number and incident atrial fibrillation |
| title_full | Mitochondrial DNA copy number and incident atrial fibrillation |
| title_fullStr | Mitochondrial DNA copy number and incident atrial fibrillation |
| title_full_unstemmed | Mitochondrial DNA copy number and incident atrial fibrillation |
| title_short | Mitochondrial DNA copy number and incident atrial fibrillation |
| title_sort | mitochondrial dna copy number and incident atrial fibrillation |
| topic | Mitochondria DNA copy number mtDNA Atrial fibrillation |
| url | http://link.springer.com/article/10.1186/s12916-020-01715-6 |
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