Mild decrease in TBX20 promoter activity is a potentially protective factor against congenital heart defects in the Han Chinese population.
Li-Wei Yu,Feng Wang,Xue-Yan Yang,Shu-Na Sun,Yufang Zheng,Bin-Bin Li,Yonghao Gui,Hongyan Wang +7 more
TL;DR: The results indicate that a moderately lower TBX20 activity potentially reduces CHD risk in the Han Chinese population, providing new insight in the study of CHD etiology.
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Abstract: Congenital heart defects (CHDs) are one of the most common human birth defects worldwide. TBX20 is a crucial transcription factor for the development of embryonic cardiovascular system. Previous studies have demonstrated that mutations in the TBX20 coding region contribute to familial and sporadic CHD occurrence. However, it remains largely unknown whether variants in the TBX20 regulatory region are also related to CHDs. In this study, we sequenced the 2 kb region upstream of the TBX20 transcription start site in 228 CHD patients and 292 controls in a Han Chinese population. Among the 8 single nucleotide polymorphisms (SNPs) identified, six SNPs are in strong linkage disequilibrium and the minor alleles are associated with lower CHD risk (for rs10235849 chosen as tag SNP, p = 0.0069, OR (95% CI) = 0.68 (0.51–0.90)). Functional analysis showed that the minor alleles have lower transcriptional activity than major alleles in both human heart tissues and three cell lines. The electrophoretic mobility shift assay suggested that TBX20 minor alleles may exhibit higher binding affinity with certain transcription repressors. Our results indicate that a moderately lower TBX20 activity potentially reduces CHD risk in the Han Chinese population, providing new insight in the study of CHD etiology.
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Multi-omic QTL mapping in early developmental tissues reveals phenotypic and temporal complexity of regulatory variants underlying GWAS loci
Timothy D. Arthur,Jennifer Nguyen,Agnieszka D'Antonio-Chronowska,Jeffrey Jaureguy,Nayara S. Silva,Benjamin Henson,Athanasia D. Panopoulos,Juan Carlos Izpisua Belmonte,Matteo D’Antonio,Graham McVicker,Kelly A. Frazer +10 more
TL;DR: One of the largest multi-omic QTL studies to date is conducted, demonstrating that many GWAS loci exhibit phenotypic complexity and therefore, are missed by traditional eQTL analyses.
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A regulatory variant in TBX2 promoter is related to the decreased susceptibility of congenital heart disease in the Han Chinese population
TL;DR: The relationship between common genetic variants in the promoter region of TBX2 gene and the risk of congenital heart disease (CHD) is determined.
2
Upregulated of TBX1 by genetic variants are associated with human congenital heart disease
TL;DR: Wang et al. as mentioned in this paper found that a higher TBX1 expression level or activity is associated with CHD susceptibility, which could affect TBX 1 downstream targets and thus disrupt the balance of the complex regulation network during cardiogenesis.
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