Jan 31, 2018

An integrative functional genomics framework for effective identification of novel regulatory variants in genome-phenome studies

Genome Medicine
Junfei ZhaoZhongming Zhao

Abstract

Genome-phenome studies have identified thousands of variants that are statistically associated with disease or traits; however, their functional roles are largely unclear. A comprehensive investigation of regulatory mechanisms and the gene regulatory networks between phenome-wide association study (PheWAS) and genome-wide association study (GWAS) is needed to identify novel regulatory variants contributing to risk for human diseases. In this study, we developed an integrative functional genomics framework that maps 215,107 significant single nucleotide polymorphism (SNP) traits generated from the PheWAS Catalog and 28,870 genome-wide significant SNP traits collected from the GWAS Catalog into a global human genome regulatory map via incorporating various functional annotation data, including transcription factor (TF)-based motifs, promoters, enhancers, and expression quantitative trait loci (eQTLs) generated from four major functional genomics databases: FANTOM5, ENCODE, NIH Roadmap, and Genotype-Tissue Expression (GTEx). In addition, we performed a tissue-specific regulatory circuit analysis through the integration of the identified regulatory variants and tissue-specific gene expression profiles in 7051 samples across 32 tiss...Continue Reading

  • References77
  • Citations2

References

  • References77
  • Citations2

Citations

Mentioned in this Paper

Genome-Wide Association Study
Study
Quantitative Trait Loci
Genome
Genes
Granulocyte Colony-Stimulating Factor
Tissue Specificity
Tissue-Specific Gene Expression
Promoter
Alzheimer's Disease

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