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DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation

BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and post-operative atrial fibrillation (POAF) is a major healthcare burden, contributing to an increased risk of stroke, kidney failure, heart attack and death. Genetic studies have identified associations with AF,...

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Autores principales: Fischer, Matthew A., Mahajan, Aman, Cabaj, Maximilian, Kimball, Todd H., Morselli, Marco, Soehalim, Elizabeth, Chapski, Douglas J., Montoya, Dennis, Farrell, Colin P., Scovotti, Jennifer, Bueno, Claudia T., Mimila, Naomi A., Shemin, Richard J., Elashoff, David, Pellegrini, Matteo, Monte, Emma, Vondriska, Thomas M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127230/
https://www.ncbi.nlm.nih.gov/pubmed/35620521
http://dx.doi.org/10.3389/fcvm.2022.837725
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author Fischer, Matthew A.
Mahajan, Aman
Cabaj, Maximilian
Kimball, Todd H.
Morselli, Marco
Soehalim, Elizabeth
Chapski, Douglas J.
Montoya, Dennis
Farrell, Colin P.
Scovotti, Jennifer
Bueno, Claudia T.
Mimila, Naomi A.
Shemin, Richard J.
Elashoff, David
Pellegrini, Matteo
Monte, Emma
Vondriska, Thomas M.
author_facet Fischer, Matthew A.
Mahajan, Aman
Cabaj, Maximilian
Kimball, Todd H.
Morselli, Marco
Soehalim, Elizabeth
Chapski, Douglas J.
Montoya, Dennis
Farrell, Colin P.
Scovotti, Jennifer
Bueno, Claudia T.
Mimila, Naomi A.
Shemin, Richard J.
Elashoff, David
Pellegrini, Matteo
Monte, Emma
Vondriska, Thomas M.
author_sort Fischer, Matthew A.
collection PubMed
description BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and post-operative atrial fibrillation (POAF) is a major healthcare burden, contributing to an increased risk of stroke, kidney failure, heart attack and death. Genetic studies have identified associations with AF, but no molecular diagnostic exists to predict POAF based on pre-operative measurements. Such a tool would be of great value for perioperative planning to improve patient care and reduce healthcare costs. In this pilot study of epigenetic precision medicine in the perioperative period, we carried out bisulfite sequencing to measure DNA methylation status in blood collected from patients prior to cardiac surgery to identify biosignatures of POAF. METHODS: We enrolled 221 patients undergoing cardiac surgery in this prospective observational study. DNA methylation measurements were obtained from blood samples drawn from awake patients prior to surgery. After controlling for clinical and methylation covariates, we analyzed DNA methylation loci in the discovery cohort of 110 patients for association with POAF. We also constructed predictive models for POAF using clinical and DNA methylation data. We subsequently performed targeted analyses of a separate cohort of 101 cardiac surgical patients to measure the methylation status solely of significant methylation loci in the discovery cohort. RESULTS: A total of 47 patients in the discovery cohort (42.7%) and 43 patients in the validation cohort (42.6%) developed POAF. We identified 12 CpGs that were statistically significant in the discovery cohort after correcting for multiple hypothesis testing. Of these sites, 6 were amenable to targeted bisulfite sequencing and chr16:24640902 was statistically significant in the validation cohort. In addition, the methylation POAF prediction model had an AUC of 0.79 in the validation cohort. CONCLUSIONS: We have identified DNA methylation biomarkers that can predict future occurrence of POAF associated with cardiac surgery. This research demonstrates the use of precision medicine to develop models combining epigenomic and clinical data to predict disease.
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spelling pubmed-91272302022-05-25 DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation Fischer, Matthew A. Mahajan, Aman Cabaj, Maximilian Kimball, Todd H. Morselli, Marco Soehalim, Elizabeth Chapski, Douglas J. Montoya, Dennis Farrell, Colin P. Scovotti, Jennifer Bueno, Claudia T. Mimila, Naomi A. Shemin, Richard J. Elashoff, David Pellegrini, Matteo Monte, Emma Vondriska, Thomas M. Front Cardiovasc Med Cardiovascular Medicine BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and post-operative atrial fibrillation (POAF) is a major healthcare burden, contributing to an increased risk of stroke, kidney failure, heart attack and death. Genetic studies have identified associations with AF, but no molecular diagnostic exists to predict POAF based on pre-operative measurements. Such a tool would be of great value for perioperative planning to improve patient care and reduce healthcare costs. In this pilot study of epigenetic precision medicine in the perioperative period, we carried out bisulfite sequencing to measure DNA methylation status in blood collected from patients prior to cardiac surgery to identify biosignatures of POAF. METHODS: We enrolled 221 patients undergoing cardiac surgery in this prospective observational study. DNA methylation measurements were obtained from blood samples drawn from awake patients prior to surgery. After controlling for clinical and methylation covariates, we analyzed DNA methylation loci in the discovery cohort of 110 patients for association with POAF. We also constructed predictive models for POAF using clinical and DNA methylation data. We subsequently performed targeted analyses of a separate cohort of 101 cardiac surgical patients to measure the methylation status solely of significant methylation loci in the discovery cohort. RESULTS: A total of 47 patients in the discovery cohort (42.7%) and 43 patients in the validation cohort (42.6%) developed POAF. We identified 12 CpGs that were statistically significant in the discovery cohort after correcting for multiple hypothesis testing. Of these sites, 6 were amenable to targeted bisulfite sequencing and chr16:24640902 was statistically significant in the validation cohort. In addition, the methylation POAF prediction model had an AUC of 0.79 in the validation cohort. CONCLUSIONS: We have identified DNA methylation biomarkers that can predict future occurrence of POAF associated with cardiac surgery. This research demonstrates the use of precision medicine to develop models combining epigenomic and clinical data to predict disease. Frontiers Media S.A. 2022-05-10 /pmc/articles/PMC9127230/ /pubmed/35620521 http://dx.doi.org/10.3389/fcvm.2022.837725 Text en Copyright © 2022 Fischer, Mahajan, Cabaj, Kimball, Morselli, Soehalim, Chapski, Montoya, Farrell, Scovotti, Bueno, Mimila, Shemin, Elashoff, Pellegrini, Monte and Vondriska. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Fischer, Matthew A.
Mahajan, Aman
Cabaj, Maximilian
Kimball, Todd H.
Morselli, Marco
Soehalim, Elizabeth
Chapski, Douglas J.
Montoya, Dennis
Farrell, Colin P.
Scovotti, Jennifer
Bueno, Claudia T.
Mimila, Naomi A.
Shemin, Richard J.
Elashoff, David
Pellegrini, Matteo
Monte, Emma
Vondriska, Thomas M.
DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation
title DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation
title_full DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation
title_fullStr DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation
title_full_unstemmed DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation
title_short DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation
title_sort dna methylation-based prediction of post-operative atrial fibrillation
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127230/
https://www.ncbi.nlm.nih.gov/pubmed/35620521
http://dx.doi.org/10.3389/fcvm.2022.837725
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