Deep learning enables genetic analysis of the human thoracic aorta.

Journal: Nature genetics
PMID: 34837083

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). Our results illustrate the potential for rapidly defining quantitative traits with deep learning, an approach that can be broadly applied to biomedical images.

Authors

  • James P Pirruccello
    Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts.
  • Mark D Chaffin
    Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA.
  • Elizabeth L Chou
    Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Stephen J Fleming
    Precision Cardiology Laboratory, The Broad Institute & Bayer US LLC, Cambridge, MA, USA.
  • Honghuang Lin
    Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  • Mahan Nekoui
    Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA.
  • Shaan Khurshid
    Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts.
  • Samuel F Friedman
    Data Sciences Platform, Broad Institute, Cambridge, MA, USA.
  • Alexander G Bick
    Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA.
  • Alessandro Arduini
    Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA.
  • Lu-Chen Weng
    Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Seung Hoan Choi
    Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA.
  • Amer-Denis Akkad
    Precision Cardiology Laboratory, The Broad Institute & Bayer US LLC, Cambridge, MA, USA.
  • Puneet Batra
    Data Sciences Platform, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Nathan R Tucker
    Masonic Medical Research Institute, Utica, NY, USA.
  • Amelia W Hall
    Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA.
  • Carolina Roselli
    Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA.
  • Emelia J Benjamin
    Framingham Heart Study, Framingham, Massachusetts.
  • Shamsudheen K Vellarikkal
    Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA.
  • Rajat M Gupta
    Department of Medicine, Divisions of Cardiovascular Medicine and Genetics, Brigham and Women's Hospital, Boston, MA, USA.
  • Christian M Stegmann
    Precision Cardiology Laboratory, The Broad Institute & Bayer US LLC, Cambridge, MA, USA.
  • Dejan Juric
    Harvard Medical School, Boston, MA, USA.
  • James R Stone
    a Department of Radiology and Medical Imaging.
  • Ramachandran S Vasan
    Framingham Heart Study, Framingham, Massachusetts.
  • Jennifer E Ho
    Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts.
  • Udo Hoffmann
    Department of Radiology, Massachusetts General Hospital, Boston.
  • Steven A Lubitz
    Cardiovascular Disease Initiative, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Anthony A Philippakis
    Data Sciences Platform, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Mark E Lindsay
    Division of Cardiology, Massachusetts General Hospital, Boston, MA, USA.
  • Patrick T Ellinor
    Cardiovascular Disease Initiative, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, Massachusetts.

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