Genetic Susceptibility to Atrial Fibrillation Identified via Deep Learning of 12-Lead Electrocardiograms

Circ Genom Precis Med. 2023 Aug;16(4):340-349. doi: 10.1161/CIRCGEN.122.003808. Epub 2023 Jun 6.

Abstract

Background: Artificial intelligence (AI) models applied to 12-lead ECG waveforms can predict atrial fibrillation (AF), a heritable and morbid arrhythmia. However, the factors forming the basis of risk predictions from AI models are usually not well understood. We hypothesized that there might be a genetic basis for an AI algorithm for predicting the 5-year risk of new-onset AF using 12-lead ECGs (ECG-AI)-based risk estimates.

Methods: We applied a validated ECG-AI model for predicting incident AF to ECGs from 39 986 UK Biobank participants without AF. We then performed a genome-wide association study (GWAS) of the predicted AF risk and compared it with an AF GWAS and a GWAS of risk estimates from a clinical variable model.

Results: In the ECG-AI GWAS, we identified 3 signals (P<5×10-8) at established AF susceptibility loci marked by the sarcomeric gene TTN and sodium channel genes SCN5A and SCN10A. We also identified 2 novel loci near the genes VGLL2 and EXT1. In contrast, the clinical variable model prediction GWAS indicated a different genetic profile. In genetic correlation analysis, the prediction from the ECG-AI model was estimated to have a higher correlation with AF than that from the clinical variable model.

Conclusions: Predicted AF risk from an ECG-AI model is influenced by genetic variation implicating sarcomeric, ion channel and body height pathways. ECG-AI models may identify individuals at risk for disease via specific biological pathways.

Keywords: algorithm; artificial intelligence; atrial fibrillation; morbidity; risk factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Artificial Intelligence
  • Atrial Fibrillation* / diagnosis
  • Atrial Fibrillation* / genetics
  • Deep Learning*
  • Electrocardiography
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans