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Identifying Genetic Factors That Contribute To The Increased Risk Of Congenital Heart Defects In Infants With Down Syndrome, Cristina E. Trevino, Aaron M. Holleman, Holly Corbitt, Cheryl L. Maslen, Tracie C. Rosser, David J. Cutler, H. Richard Johnston, Benjamin L. Rambo-Martin, Jai Oberoi, Kenneth J. Dooley, George T. Capone, Roger H. Reeves, Heather J. Cordell, Bernard D. Keavney, A. J. Agopian, Elizabeth Goldmuntz, Peter J. Gruber, James O'Brien, Douglas Bittel, Lalita Wadhwa, Clifford L. Cua, Ivan P. Moskowitz, Jennifer G. Mulle, Michael P. Epstein, Stephanie L. Sherman, Michael E. Zwick

Faculty Publications

Atrioventricular septal defects (AVSD) are a severe congenital heart defect present in individuals with Down syndrome (DS) at a > 2000-fold increased prevalence compared to the general population. This study aimed to identify risk-associated genes and pathways and to examine a potential polygenic contribution to AVSD in DS. We analyzed a total cohort of 702 individuals with DS with or without AVSD, with genomic data from whole exome sequencing, whole genome sequencing, and/or array-based imputation. We utilized sequence kernel association testing and polygenic risk score (PRS) methods to examine rare and common variants. Our findings suggest that the Notch pathway, particularly …