GWAS3D

Detecting human regulatory variants by integrative analysis of genome-wide associations, chromosome interactions and histone modifications.

Mulin Jun Li, Lily Yan Wang, Zhengyuan Xia, Pak Chung Sham, Junwen Wang

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Interpreting the genetic variants located in the regulatory regions, such as enhancers and promoters, is an indispensable step to understand molecular mechanism of complex traits. Recent studies show that genetic variants detected by genome-wide association study (GWAS) are significantly enriched in the regulatory regions. Therefore, detecting, annotating and prioritizing of genetic variants affecting gene regulation are critical to our understanding of genotype-phenotype relationships. Here, we developed a web server GWAS3D to systematically analyze the genetic variants that could affect regulatory elements, by integrating annotations from cell type-specific chromatin states, epigenetic modifications, sequence motifs and cross-species conservation. The regulatory elements are inferred from the genome-wide chromosome interaction data, chromatin marks in 16 different cell types and 73 regulatory factors motifs from the Encyclopedia of DNA Element project. Furthermore, we used these function elements, as well as risk haplotype, binding affinity, conservation and P-values reported from the original GWAS to reprioritize the genetic variants. Using studies from low-density lipoprotein cholesterol, we demonstrated that our reprioritizing approach was effective and cell type specific. In conclusion, GWAS3D provides a comprehensive annotation and visualization tool to help users interpreting their results. The web server is freely available at http://jjwanglab.org/gwas3d.

Original languageEnglish (US)
JournalNucleic Acids Research
Volume41
Issue numberWeb Server issue
DOIs
StatePublished - Jul 2013
Externally publishedYes

Fingerprint

Histone Code
Genome-Wide Association Study
Chromosomes
Nucleic Acid Regulatory Sequences
Chromatin
Encyclopedias
Nucleotide Motifs
Epigenomics
LDL Cholesterol
Haplotypes
Genotype
Genome
Phenotype
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

GWAS3D : Detecting human regulatory variants by integrative analysis of genome-wide associations, chromosome interactions and histone modifications. / Li, Mulin Jun; Wang, Lily Yan; Xia, Zhengyuan; Sham, Pak Chung; Wang, Junwen.

In: Nucleic Acids Research, Vol. 41, No. Web Server issue, 07.2013.

Research output: Contribution to journalArticle

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