Affiliation:
1. Cardio Diagnostics Inc Chicago IL USA
2. Department of Psychiatry University of Iowa Iowa City IA USA
3. Department of Biomedical Engineering University of Iowa Iowa City IA USA
4. Intermountain Heart Institute, Intermountain Healthcare Salt Lake City UT USA
5. Department of Internal Medicine University of Utah Salt Lake City UT USA
6. Division of Cardiovascular Medicine, Department of Internal Medicine University of Iowa Iowa City IA USA
7. Southern California Heart Centers San Gabriel CA USA
8. Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA
Abstract
Background
Coronary heart disease (CHD) is the leading cause of death in the world. Unfortunately, many of the key diagnostic tools for CHD are insensitive, invasive, and costly; require significant specialized infrastructure investments; and do not provide information to guide postdiagnosis therapy. In prior work using data from the Framingham Heart Study, we provided in silico evidence that integrated genetic–epigenetic tools may provide a new avenue for assessing CHD.
Methods and Results
In this communication, we use an improved machine learning approach and data from 2 additional cohorts, totaling 449 cases and 2067 controls, to develop a better model for ascertaining symptomatic CHD. Using the DNA from the 2 new cohorts, we translate and validate the in silico findings into an artificial intelligence–guided, clinically implementable method that uses input from 6 methylation‐sensitive digital polymerase chain reaction and 10 genotyping assays. Using this method, the overall average area under the curve, sensitivity, and specificity in the 3 test cohorts is 82%, 79%, and 76%, respectively. Analysis of targeted cytosine‐phospho‐guanine loci shows that they map to key risk pathways involved in atherosclerosis that suggest specific therapeutic approaches.
Conclusions
We conclude that this scalable integrated genetic–epigenetic approach is useful for the diagnosis of symptomatic CHD, performs favorably as compared with many existing methods, and may provide personalized insight to CHD therapy. Furthermore, given the dynamic nature of DNA methylation and the ease of methylation‐sensitive digital polymerase chain reaction methodologies, these findings may pave a pathway for precision epigenetic approaches for monitoring CHD treatment response.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
1 articles.
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