Genome sequencing is critical for forecasting outcomes following congenital cardiac surgery
Abstract
Abstract While exome and whole genome sequencing have transformed medicine by elucidating the genetic underpinnings of both rare and common complex disorders, its utility to predict clinical outcomes remains understudied. Here, we use artificial intelligence (AI) technologies to explore the predictive value of whole exome sequencing in forecasting clinical outcomes following surgery for congenital heart defects (CHD). We report results for a prospective observational cohort study of 2,253 CHD patients from the Pediatric Cardiac Genomics Consortium with a broad range of complex heart defects, pre- and post-operative clinical variables and exome sequencing. Damaging genotypes in chromatin-modifying and cilia-related genes are associated with an elevated risk of adverse post-operative outcomes, including mortality, cardiac arrest and prolonged mechanical ventilation. The impact of damaging genotypes is further amplified in the context of specific CHD phenotypes, surgical complexity and extra-cardiac anomalies. The absence of a damaging genotype in chromatin-modifying and cilia-related genes is also informative, reducing the risk for some adverse postoperative outcomes. Thus, genome sequencing enriches the ability to forecast outcomes following congenital cardiac surgery.
Article Details
Authors (26)
W. Scott Watkins
Edgar J. Hernandez
Thomas A. Miller
Nathan R. Blue
Raquel Mae Zimmerman
Eric R. Griffiths
Erwin Frise
Daniel Bernstein
Department of Pediatrics, Cardiology, Stanford University
Marko T. Boskovski
Martina Brueckner
Department of Genetics, Yale School of Medicine
Wendy K. Chung
Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School
J. William Gaynor
Division of Cardiothoracic Surgery, Children's Hospital of Philadelphia
Bruce D. Gelb
Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai
Elizabeth Goldmuntz
Division of Cardiology, Children’s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania
Peter J. Gruber
Department of Surgery, Yale University School of Medicine
Jane W. Newburger
Department of Cardiology, Boston Children’s Hospital, Harvard Medical School
Amy E. Roberts
Department of Cardiology, Boston Children’s Hospital, Harvard Medical School
Sarah U. Morton
Division of Newborn Medicine, Department of Pediatrics, Boston Children’s Hospital
John E. Mayer
Christine E. Seidman
Jonathan G. Seidman
Yufeng Shen
Department of Systems Biology, Columbia University Irving Medical Center
Michael Wagner
H. Joseph Yost
Department of Human Genetics, University of Utah and School of Medicine
Mark Yandell
Department of Human Genetics, University of Utah and School of Medicine
Martin Tristani-Firouzi
Division of Pediatric Cardiology, University of Utah