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Epigenetic Age and the Risk of Incident Atrial Fibrillation.
Roberts, Jason D; Vittinghoff, Eric; Lu, Ake T; Alonso, Alvaro; Wang, Biqi; Sitlani, Colleen M; Mohammadi-Shemirani, Pedrum; Fornage, Myriam; Kornej, Jelena; Brody, Jennifer A; Arking, Dan E; Lin, Honghuang; Heckbert, Susan R; Prokic, Ivana; Ghanbari, Mohsen; Skanes, Allan C; Bartz, Traci M; Perez, Marco V; Taylor, Kent D; Lubitz, Steven A; Ellinor, Patrick T; Lunetta, Kathryn L; Pankow, James S; Paré, Guillaume; Sotoodehnia, Nona; Benjamin, Emelia J; Horvath, Steve; Marcus, Gregory M.
Afiliación
  • Roberts JD; Population Health Research Institute (J.D.R., P.M-S., G.P.).
  • Vittinghoff E; Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, ON, Canada (J.D.R., A.C.S.).
  • Lu AT; Department of Epidemiology and Biostatistics (E.V.) University of California, San Francisco.
  • Alonso A; Department of Human Genetics, David Geffen School of Medicine (A.T.L., S.H.); University of California, Los Angeles.
  • Wang B; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA (A.A.).
  • Sitlani CM; Framingham Heart Study, Framingham, MA (B.W., J.K., H.L., E.J.B.).
  • Mohammadi-Shemirani P; Departments of Biostatistics (B.W., K.L.L.), School of Public Health.
  • Fornage M; Cardiovascular Health Research Unit (C.M.S., J.A.B., S.R.H., T.M.B., N.S.).
  • Kornej J; Medicine (C.M.S., J.A.B., T.M.B., N.S.); University of Washington, Seattle.
  • Brody JA; Population Health Research Institute (J.D.R., P.M-S., G.P.).
  • Arking DE; Departments of Medical Sciences (P.M-S.), McMaster University, Hamilton, ON, Canada.
  • Lin H; Thrombosis and Atherosclerosis Research Institute, Department of Medicine, David Braley Cardiac, Vascular, and Stroke Research Institute (P.M-S., G.P.); McMaster University, Hamilton, ON, Canada.
  • Heckbert SR; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston (M.F.).
  • Prokic I; Framingham Heart Study, Framingham, MA (B.W., J.K., H.L., E.J.B.).
  • Ghanbari M; Sections of Cardiovascular Medicine (J.K., E.J.B.), Department of Medicine, School of Medicine; Boston University, MA.
  • Skanes AC; Cardiovascular Health Research Unit (C.M.S., J.A.B., S.R.H., T.M.B., N.S.).
  • Bartz TM; Medicine (C.M.S., J.A.B., T.M.B., N.S.); University of Washington, Seattle.
  • Perez MV; McKusick-Nathans Institute, Department of Genetic Medicine, Baltimore, MD (D.E.A.).
  • Taylor KD; Framingham Heart Study, Framingham, MA (B.W., J.K., H.L., E.J.B.).
  • Lubitz SA; Computational Biomedicine (H.L.), Department of Medicine, School of Medicine; Boston University, MA.
  • Ellinor PT; Cardiovascular Health Research Unit (C.M.S., J.A.B., S.R.H., T.M.B., N.S.).
  • Lunetta KL; Departments of Epidemiology (S.R.H., N.S.), University of Washington, Seattle.
  • Pankow JS; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands (I.P., M.G.).
  • Paré G; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands (I.P., M.G.).
  • Sotoodehnia N; Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, ON, Canada (J.D.R., A.C.S.).
  • Benjamin EJ; Cardiovascular Health Research Unit (C.M.S., J.A.B., S.R.H., T.M.B., N.S.).
  • Horvath S; Biostatistics (T.M.B.), University of Washington, Seattle.
  • Marcus GM; Medicine (C.M.S., J.A.B., T.M.B., N.S.); University of Washington, Seattle.
Circulation ; 144(24): 1899-1911, 2021 12 14.
Article en En | MEDLINE | ID: mdl-34587750
BACKGROUND: The most prominent risk factor for atrial fibrillation (AF) is chronological age; however, underlying mechanisms are unexplained. Algorithms using epigenetic modifications to the human genome effectively predict chronological age. Chronological and epigenetic predicted ages may diverge in a phenomenon referred to as epigenetic age acceleration (EAA), which may reflect accelerated biological aging. We sought to evaluate for associations between epigenetic age measures and incident AF. METHODS: Measures for 4 epigenetic clocks (Horvath, Hannum, DNA methylation [DNAm] PhenoAge, and DNAm GrimAge) and an epigenetic predictor of PAI-1 (plasminogen activator inhibitor-1) levels (ie, DNAm PAI-1) were determined for study participants from 3 population-based cohort studies. Cox models evaluated for associations with incident AF and results were combined via random-effects meta-analyses. Two-sample summary-level Mendelian randomization analyses evaluated for associations between genetic instruments of the EAA measures and AF. RESULTS: Among 5600 participants (mean age, 65.5 years; female, 60.1%; Black, 50.7%), there were 905 incident AF cases during a mean follow-up of 12.9 years. Unadjusted analyses revealed all 4 epigenetic clocks and the DNAm PAI-1 predictor were associated with statistically significant higher hazards of incident AF, though the magnitudes of their point estimates were smaller relative to the associations observed for chronological age. The pooled EAA estimates for each epigenetic measure, with the exception of Horvath EAA, were associated with incident AF in models adjusted for chronological age, race, sex, and smoking variables. After multivariable adjustment for additional known AF risk factors that could also potentially function as mediators, pooled EAA measures for 2 clocks remained statistically significant. Five-year increases in EAA measures for DNAm GrimAge and DNAm PhenoAge were associated with 19% (adjusted hazard ratio [HR], 1.19 [95% CI, 1.09-1.31]; P<0.01) and 15% (adjusted HR, 1.15 [95% CI, 1.05-1.25]; P<0.01) higher hazards of incident AF, respectively. Mendelian randomization analyses for the 5 EAA measures did not reveal statistically significant associations with AF. CONCLUSIONS: Our study identified adjusted associations between EAA measures and incident AF, suggesting that biological aging plays an important role independent of chronological age, though a potential underlying causal relationship remains unclear. These aging processes may be modifiable and not constrained by the immutable factor of time.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Envejecimiento / Metilación de ADN / Epigénesis Genética / Modelos Cardiovasculares / Modelos Genéticos Tipo de estudio: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Circulation Año: 2021 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Envejecimiento / Metilación de ADN / Epigénesis Genética / Modelos Cardiovasculares / Modelos Genéticos Tipo de estudio: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Circulation Año: 2021 Tipo del documento: Article