Deep learning enables genetic analysis of the human thoracic aorta

Nat Genet. 2022 Jan;54(1):40-51. doi: 10.1038/s41588-021-00962-4. Epub 2021 Nov 26.

Abstract

Enlargement or aneurysm of the aorta predisposes to dissection, an important cause of sudden death. We trained a deep learning model to evaluate the dimensions of the ascending and descending thoracic aorta in 4.6 million cardiac magnetic resonance images from the UK Biobank. We then conducted genome-wide association studies in 39,688 individuals, identifying 82 loci associated with ascending and 47 with descending thoracic aortic diameter, of which 14 loci overlapped. Transcriptome-wide analyses, rare-variant burden tests and human aortic single nucleus RNA sequencing prioritized genes including SVIL, which was strongly associated with descending aortic diameter. A polygenic score for ascending aortic diameter was associated with thoracic aortic aneurysm in 385,621 UK Biobank participants (hazard ratio = 1.43 per s.d., confidence interval 1.32-1.54, P = 3.3 × 10-20). Our results illustrate the potential for rapidly defining quantitative traits with deep learning, an approach that can be broadly applied to biomedical images.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aorta, Thoracic / anatomy & histology*
  • Aorta, Thoracic / pathology
  • Aortic Aneurysm / genetics
  • Aortic Aneurysm / pathology
  • Biological Variation, Population
  • Deep Learning*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Quantitative Trait Loci
  • Transcriptome