Faculty, Staff and Student Publications
Publication Date
1-21-2022
Journal
Circulation Research
Abstract
RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored.
OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA.
METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10
CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near
Keywords
Animals, Cells, Cultured, Humans, Mice, Multifactorial Inheritance, Myocytes, Cardiac, Polymorphism, Single Nucleotide, T-Box Domain Proteins, Transposition of Great Vessels, Wnt-5a Protein, Zebrafish
DOI
10.1161/CIRCRESAHA.120.317107
PMID
34886679
PMCID
PMC8768504
PubMedCentral® Posted Date
12-10-2021
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes