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

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