Congenital heart disease risk loci identified by genome-wide association study in European patients.
Cardiology
Cardiovascular disease
Genetics
Molecular genetics
iPS cells
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
19 01 2021
19 01 2021
Historique:
received:
30
06
2020
accepted:
12
11
2020
pubmed:
18
11
2020
medline:
10
9
2021
entrez:
17
11
2020
Statut:
ppublish
Résumé
Genetic factors undoubtedly affect the development of congenital heart disease (CHD) but still remain ill defined. We sought to identify genetic risk factors associated with CHD and to accomplish a functional analysis of SNP-carrying genes. We performed a genome-wide association study (GWAS) of 4034 White patients with CHD and 8486 healthy controls. One SNP on chromosome 5q22.2 reached genome-wide significance across all CHD phenotypes and was also indicative for septal defects. One region on chromosome 20p12.1 pointing to the MACROD2 locus identified 4 highly significant SNPs in patients with transposition of the great arteries (TGA). Three highly significant risk variants on chromosome 17q21.32 within the GOSR2 locus were detected in patients with anomalies of thoracic arteries and veins (ATAV). Genetic variants associated with ATAV are suggested to influence the expression of WNT3, and the variant rs870142 related to septal defects is proposed to influence the expression of MSX1. We analyzed the expression of all 4 genes during cardiac differentiation of human and murine induced pluripotent stem cells in vitro and by single-cell RNA-Seq analyses of developing murine and human hearts. Our data show that MACROD2, GOSR2, WNT3, and MSX1 play an essential functional role in heart development at the embryonic and newborn stages.
Identifiants
pubmed: 33201861
pii: 141837
doi: 10.1172/JCI141837
pmc: PMC7810487
doi:
pii:
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : British Heart Foundation
ID : CH/13/2/30154
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/15/12/31616
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/F/21/110050
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
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