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

The Journal of Clinical Investigation
Harald LahmMarkus Krane

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 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, ...Continue Reading

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Citations

Jan 20, 2021·The Journal of Clinical Investigation·Dawood Darbar
Feb 14, 2021·Cells·Kerryanne CrawfordIvan Ahel
Jul 3, 2021·Genes·Nicholas S DiabSheng Chih Jin
Oct 8, 2021·BMC Developmental Biology·Ramada R KhasawnehSimon D Bamforth

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Datasets Mentioned

BETA
GSE126128
GSE161016

Methods Mentioned

BETA
RNA-Seq
genotyping
transgenic
scRNA-Seq
chip
PCR
FCS
FACS
dissection
PCA

Software Mentioned

ClustVis
Galaxy
Axiom
CAVIARBF
FeatureCounts
Genomics CellRanger
ClueGO
. PC
Analysis Suite
SigmaPlot

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