Document Type
Article
Publication Date
1-21-2022
Publication Title
Circulation research
Keywords
JMG, Animals, Cells, Cultured, Humans, Mice, Multifactorial Inheritance, Myocytes, Cardiac, Polymorphism, Single Nucleotide, T-Box Domain Proteins, Transposition of Great Vessels, Wnt-5a Protein, Zebrafish
JAX Source
Circ Res 2022 Jan 21; 130(2):166-180
Volume
130
Issue
2
First Page
166
Last Page
180
ISSN
1524-4571
PMID
34886679
DOI
https://doi.org/10.1161/circresaha.120.317107
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
Recommended Citation
Škorić-Milosavljević D,
Tadros R,
Bosada F,
Tessadori F,
van Weerd J,
Woudstra O,
Tjong F,
Lahrouchi N,
Bajolle F,
Cordell H,
Agopian A,
Blue G,
Barge-Schaapveld D,
Gewillig M,
Preuss C,
Lodder E,
Barnett P,
Ilgun A,
Beekman L,
van Duijvenboden K,
Bokenkamp R,
Müller-Nurasyid M,
Vliegen H,
Konings T,
van Melle J,
van Dijk A,
van Kimmenade R,
Roos-Hesselink J,
Sieswerda G,
Meijboom F,
Abdul-Khaliq H,
Berger F,
Dittrich S,
Hitz M,
Moosmann J,
Riede F,
Schubert S,
Galan P,
Lathrop M,
Munter H,
Al-Chalabi A,
Shaw C,
Shaw P,
Morrison K,
Veldink J,
van den Berg L,
Evans S,
Nobrega M,
Aneas I,
Radivojkov-Blagojević M,
Meitinger T,
Oechslin E,
Mondal T,
Bergin L,
Smythe J,
Altamirano-Diaz L,
Lougheed J,
Bouma B,
Chaix M,
Kline J,
Bassett A,
Andelfinger G,
van der Palen R,
Bouvagnet P,
Clur S,
Breckpot J,
Kerstjens-Frederikse W,
Winlaw D,
Bauer U,
Mital S,
Goldmuntz E,
Keavney B,
Bonnet D,
Mulder B,
Tanck M,
Bakkers J,
Christoffels V,
Boogerd C,
Postma A,
Bezzina C.
Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries. Circ Res 2022 Jan 21; 130(2):166-180
Comments
This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License.