Common genetic variants improve risk stratification after atrial switch operation for transposition of the great arteries

Abstract Background Current clinical risk scores are able to predict late complication risk in adults after atrial switch operation (AtrSO) for transposition of the great arteries (TGA), but a large heterogeneity in clinical course remains. Purpose To study whether common genetic factors are predictive of outcome and provide added value to an existing clinical risk score in TGA-AtrSO patients. Methods This multicenter study examined the association of genome-wide single-nucleotide polymorphisms (SNPs) in TGA-AtrSO patients with a combined clinical endpoint: time to symptomatic ventricular arrhythmia, heart failure hospitalization, ventricular assist device implantation, heart transplantation, or mortality. Furthermore, we evaluated whether a polygenic risk score (PRS) constructed of independent single-nucleotide polymorphisms (SNPs) with a p30 years, prior ventricular arrhythmia, age >1 year at repair, ≥moderate right ventricular dysfunction, severe tricuspid regurgitation, and ≥mild left ventricular dysfunction). Results We followed 133 patients (age at inclusion 28 [IQR 24–35] years, 59% male) for 13 [IQR 8–16] years. Thirty-two patients (24%) reached the endpoint. The genome-wide association study yielded one locus that reached genome-wide significance (p