| dc.description.abstract | Congenital heart defects affect 40,000 US births per year, half of which require surgical intervention. Individual differences in surgical outcomes including mortality and complications are not well understood but may be due to genetic variability. We hypothesized that polygenic risk scores for blood pressure in adults are associated with treatments and post-surgical outcomes in children with congenital heart defects, as congenital heart defect survivors are at higher risk of negative cardiometabolic disease. We used imputed genotype data from pediatric participants requiring surgery for congenital heart defects (median age at surgery = 201 days, nmax = 2,498). Base data for the systolic and diastolic blood pressure polygenic risk scores (nmax = 760,226) came from published genome-wide association study. The blood pressure polygenic risk scores were tested for association with post-surgical outcomes. All effects presented are per standard deviation increase in polygenic risk score and adjusted for age, sex, body mass index, surgical complexity score, and first ten principal components of ancestry. A higher diastolic blood pressure polygenic risk score was associated with decreased in-hospital mortality risk (OR = 0.57 (0.39 – 0.82), p = 0.0022). Additional analyses suggest an interaction between diastolic blood pressure polygenic risk score and vasopressor dose. Those with a diastolic blood pressure polygenic risk score one standard deviation above the mean, receiving a vasopressor dose in the top tertile, were estimated to have 52% (32% – 66%) lower risk of in-hospital mortality compared to those with a vasopressor dose in the bottom tertile. These results suggest a genetically determined post-surgical survival advantage for congenital heart defect patients with blood pressure increasing alleles. Further study may reveal novel mechanisms contributing to post-operative morbidity and mortality, and this approach may assist in early identification of children at risk for adverse post-operative outcomes. | |
