VSEAMS: a pipeline for variant set enrichment analysis using summary GWAS data identifies IKZF3, BATF and ESRRA as key transcription factors in type 1 diabetes
نویسندگان
چکیده
MOTIVATION Genome-wide association studies (GWAS) have identified many loci implicated in disease susceptibility. Integration of GWAS summary statistics (P-values) and functional genomic datasets should help to elucidate mechanisms. RESULTS We extended a non-parametric SNP set enrichment method to test for enrichment of GWAS signals in functionally defined loci to a situation where only GWAS P-values are available. The approach is implemented in VSEAMS, a freely available software pipeline. We use VSEAMS to identify enrichment of type 1 diabetes (T1D) GWAS associations near genes that are targets for the transcription factors IKZF3, BATF and ESRRA. IKZF3 lies in a known T1D susceptibility region, while BATF and ESRRA overlap other immune disease susceptibility regions, validating our approach and suggesting novel avenues of research for T1D. AVAILABILITY AND IMPLEMENTATION VSEAMS is available for download (http://github.com/ollyburren/vseams).
منابع مشابه
Original Contribution Integrating Genetic Association, Genetics of Gene Expression, and Single Nucleotide Polymorphism Set Analysis to Identify Susceptibility Loci for Type 2 Diabetes Mellitus
Large-scale genome-wide association studies (GWAS) have identified over 40 genomic regions significantly associated with type 2 diabetes mellitus. However, GWAS results are not always straightforward to interpret, and linking these loci to meaningful disease etiology is often difficult without extensive follow-up studies. The authors expanded on previously reported type 2 diabetes mellitus GWAS...
متن کاملGenetics of Type 2 Diabetes- A Review Article
Objective: Type 2 diabetes (T2D) as a complex disease is the result of genetically heterogeneous factors and environmental issues interaction. Linkage and small-scale candidate gene studies were successful in identification of genetic susceptibilities of monogenic form of diseases. However, they were largely unsuccessful while applying to the more common forms of disease. By designing Genome Wi...
متن کاملGenetic control of gene expression at novel and established chronic obstructive pulmonary disease loci.
Genetic risk loci have been identified for a wide range of diseases through genome-wide association studies (GWAS), but the relevant functional mechanisms have been identified for only a small proportion of these GWAS-identified loci. By integrating results from the largest current GWAS of chronic obstructive disease (COPD) with expression quantitative trait locus (eQTL) analysis in whole blood...
متن کاملIntegrating Genome-Wide Association and eQTLs Studies Identifies the Genes and Gene Sets Associated with Diabetes
AIM To identify novel candidate genes and gene sets for diabetes. METHODS We performed an integrative analysis of genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) data for diabetes. Summary data was driven from a large-scale GWAS of diabetes, totally involving 58,070 individuals. eQTLs dataset included 923,021 cis-eQTL for 14,329 genes and 4,732 trans-eQTL...
متن کاملPathways Targeted by Antidiabetes Drugs Are Enriched for Multiple Genes Associated With Type 2 Diabetes Risk
Genome-wide association studies (GWAS) have uncovered >65 common variants associated with type 2 diabetes (T2D); however, their relevance for drug development is not yet clear. Of note, the first two T2D-associated loci (PPARG and KCNJ11/ABCC8) encode known targets of antidiabetes medications. We therefore tested whether other genes/pathways targeted by antidiabetes drugs are associated with T2...
متن کامل