Genome-Wide Association Studies of Down Syndrome Associated Congenital Heart Defects Suggests a Genetically Heterogeneous Risk for CHD in DS.
Feldman ER., Li Y., Cutler DJ., Rosser TC., Wechsler SB., Sanclemente L., Rachubinski AL., Elliott N., Vyas P., Roberts I., Rabin KR., Wagner M., Gelb BD., Espinosa JM., Lupo PJ., de Smith AJ., Sherman SL., Leslie-Clarkson EJ.
Congenital heart defects (CHDs) are the most common structural birth defect and are present in 40%-50% of children born with Down syndrome (DS). To characterize the genetic architecture of DS-associated CHD, we sequenced genomes of a multiethnic group of children with DS and a CHD (n = 886: atrioventricular septal defects (AVSD), n = 438; atrial septal defects (ASD), n = 122; ventricular septal defects (VSD), n = 170; other types of CHD, n = 156) and DS with a structurally normal heart (DS + NH, n = 572). We performed four genome-wide association study (GWAS) for common variants (MAF > 0.05) comparing DS with CHD, stratified by CHD-subtype, to DS + NH controls. Although no SNP achieved genome-wide significance, multiple loci in each analysis achieved suggestive significance (p