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, Doris; Tadros, Rafik; Bosada, Fernanda M; Tessadori, Federico; van Weerd, Jan Hendrik; Woudstra, Odilia I; Tjong, Fleur V Y; Lahrouchi, Najim; Bajolle, Fanny; Cordell, Heather J; Agopian, A J; Blue, Gillian M; Barge-Schaapveld, Daniela Q C M; Gewillig, Marc; Preuss, Christoph; Lodder, Elisabeth M; Barnett, Phil; Ilgun, Aho; Beekman, Leander; van Duijvenboden, Karel; Bokenkamp, Regina; Müller-Nurasyid, Martina; Vliegen, Hubert W; Konings, Thelma C; van Melle, Joost P; van Dijk, Arie P J; van Kimmenade, Roland R J; Roos-Hesselink, Jolien W; Sieswerda, Gertjan T; Meijboom, Folkert; Abdul-Khaliq, Hashim; Berger, Felix; Dittrich, Sven; Hitz, Marc-Phillip; Moosmann, Julia; Riede, Frank-Thomas; Schubert, Stephan; Galan, Pilar; Lathrop, Mark; Munter, Hans M; Al-Chalabi, Ammar; Shaw, Christopher E; Shaw, Pamela J; Morrison, Karen E; Veldink, Jan H; van den Berg, Leonard H; Evans, Sylvia; Nobrega, Marcelo A; Aneas, Ivy; Radivojkov-Blagojević, Milena; Meitinger, Thomas; Oechslin, Erwin; Mondal, Tapas; Bergin, Lynn; Smythe, John F; Altamirano-Diaz, Luis; Lougheed, Jane; Bouma, Berto J; Chaix, Marie-A; Kline, Jennie; Bassett, Anne S; Andelfinger, Gregor; van der Palen, Roel L F; Bouvagnet, Patrice; Clur, Sally-Ann B; Breckpot, Jeroen; Kerstjens-Frederikse, Wilhelmina S; Winlaw, David S; Bauer, Ulrike M M; Mital, Seema; Goldmuntz, Elizabeth; Keavney, Bernard; Bonnet, Damien; Mulder, Barbara J; Tanck, Michael W T; Bakkers, Jeroen; Christoffels, Vincent M; Boogerd, Cornelis J; Postma, Alex V; and Bezzina, Connie R, "Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries." (2022). Faculty Research 2022. 33.
https://mouseion.jax.org/stfb2022/33
Comments
This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License.