Decoding the Genomics of Abdominal Aortic Aneurysm

Cell. 2018 Sep 6;174(6):1361-1372.e10. doi: 10.1016/j.cell.2018.07.021.


A key aspect of genomic medicine is to make individualized clinical decisions from personal genomes. We developed a machine-learning framework to integrate personal genomes and electronic health record (EHR) data and used this framework to study abdominal aortic aneurysm (AAA), a prevalent irreversible cardiovascular disease with unclear etiology. Performing whole-genome sequencing on AAA patients and controls, we demonstrated its predictive precision solely from personal genomes. By modeling personal genomes with EHRs, this framework quantitatively assessed the effectiveness of adjusting personal lifestyles given personal genome baselines, demonstrating its utility as a personal health management tool. We showed that this new framework agnostically identified genetic components involved in AAA, which were subsequently validated in human aortic tissues and in murine models. Our study presents a new framework for disease genome analysis, which can be used for both health management and understanding the biological architecture of complex diseases. VIDEO ABSTRACT.

Keywords: HEAL; abdominal aortic aneurysm; cardiovascular diseases; complex disease; electronic health record; lifestyle; machine learning; personal genome; personal health management; precision medicine.

Publication types

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

MeSH terms

  • Animals
  • Aortic Aneurysm, Abdominal / genetics
  • Aortic Aneurysm, Abdominal / pathology*
  • Area Under Curve
  • Disease Models, Animal
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Genome-Wide Association Study
  • Genomics*
  • Humans
  • Machine Learning
  • Mice
  • Polymorphism, Single Nucleotide
  • Protein Interaction Maps
  • ROC Curve
  • Whole Genome Sequencing