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Year : 2018  |  Volume : 2  |  Issue : 4  |  Page : 269-275

Using postgenome-wide association study analysis; Vars2-Pic3ca-AKT is novel putative interactive pathway associated with conotruncal heart defects

Department of Molecular Genetics and Enzymology, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt

Correspondence Address:
Dr. Alaaeldin Fayez
Department of Molecular Genetics and Enzymology, Division of Human Genetics and Genome Research, National Research Centre, Cairo
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bbrj.bbrj_106_18

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Background: Genome-wide association studies (GWASs) have identified 43-associated variants with conotruncal heart defects (CTD) at P ≤ 5E-7, P ≤ 5E-6, and P ≤ 5E-5 till January 2018. Despite the GWASs still provide a growing number of associated genetic variants, the identification of their pathogenic mechanisms remains a major challenge in human genetics requiring data mining efforts and predictive models for accurate interpretation of noncoding variants especially. Hence, I applied a post-GWAS analysis approach to identify the possible mechanism of action of noncoding variants associated with CTD according to the latest update of the GWAS catalog. Method: I aimed in this study to conduct a post-GWAS analysis of the most associated noncoding variants with CTD to elucidate its probable pathogenic mechanisms. Through three GWAS traits belong to CTDs, it was used in a variety of integrated and computational algorithms to collect the available information about the selected noncoding variants and its associated partners. Results: It was found differential histone modification, motif binding, and gene expression among the CTD-associated single nucleotide polymorphisms. Through intensive analysis, it was also found that both the linked rs2517582 and rs17189763 haplotype might lead to alteration in the Pic3ca-AKT signal pathway due to a change of CTCF-binding affinity and upregulation of VARS2 gene. Conclusion: It was concluded that the indirect effect of the upregulation VARS2 gene might associates with CTD. Consequently, phosphoinositide 3-kinases/AKT (pic3ca/AKT) pathway has a pivotal role in the signal system of heart morphogenesis.

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