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Prioritizing long range interactions in noncoding regions using GWAS and deletions perturbed TADs.


ABSTRACT: Genome-wide association studies (GWAS) have contributed significantly to predisposing the disease etiology by associating single nucleotide polymorphisms (SNPs) with complex diseases. However, most GWAS-SNPs are in the noncoding regions that may affect distal genes via long range enhancer-promoter interactions. Thus, the common practice on GWAS discoveries cannot fully reveal the molecular mechanisms underpinning complex diseases. It is known that perturbations of topological associated domains (TADs) lead to long range interactions which underlie disease etiology. To identify the probable long range interactions in noncoding regions via GWAS and TADs perturbed by deletions, we integrated datasets from GWAS-SNPs, enhancers, TADs, and deletions. After ranking and clustering, we prioritized 201,132 high confident pairs of GWAS-SNPs and target genes. In this study, we performed a systematic inference on noncoding regions via GWAS-SNPs and deletion-perturbed TADs to boost GWAS discovery power. The high confident pairs of GWAS-SNPs and target genes (SE-Gs) provide the promising candidates to understand the molecular mechanisms underlying complex diseases with emphasis on the three-dimensional genome.

SUBMITTER: Liu X 

PROVIDER: S-EPMC7642798 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

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