Congenital heart disease risk loci identified by genome-wide association study 
in European patients

Lahm, Harald; Jia, Meiwen; Dressen, Martina; Wirth, Felix; Puluca, Nazan; Gilsbach, Ralf; Keavney, Bernard D.; Cleuziou, Julie; Beck, Nicole; Bondareva, Olga; Dzilic, Elda; Burri, Melchior; Konig, Karl C.; Ziegelmuller, Johannes A.; Abou-Ajram, Claudia; Neb, Irina; Zhang, Zhong; Doppler, Stefanie A.; Mastantuono, Elisa; Lichtner, Peter; Eckstein, Gertrud; Horer, Jurgen; Ewert, Peter; Priest, James R.; Hein, Lutz; Lange, Rudiger; Meitinger, Thomas; Cordell, Heather J.; Mueller-Myhsok, Bertram; Krane, Markus

doi:10.1172/JCI141837

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Congenital heart disease risk loci identified by genome-wide association study in European patients

MPS-Authors

/persons/resource/persons263537

Jia, Meiwen
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80450

Mueller-Myhsok, Bertram
RG Statistical Genetics, Max Planck Institute of Psychiatry, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Lahm, H., Jia, M., Dressen, M., Wirth, F., Puluca, N., Gilsbach, R., et al. (2021). Congenital heart disease risk loci identified by genome-wide association study in European patients. JOURNAL OF CLINICAL INVESTIGATION, 131(2): e141837. doi:10.1172/JCI141837.

Cite as: https://hdl.handle.net/21.11116/0000-0008-E16D-0

Abstract

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 MSX7. 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 MSX7 play an essential functional role in heart development at the embryonic and newborn stages.