GWASdb: a database for human genetic variants identified by genome-wide association studies

Abstract

Recent advances in genome-wide association studies (GWAS) have enabled us to identify thousands of genetic variants (GVs) that are associated with human diseases. As next-generation sequencing technologies become less expensive, more GVs will be discovered in the near future. Existing databases, such as NHGRI GWAS Catalog, collect GVs with only genome-wide level significance. However, many true disease susceptibility loci have relatively moderate P values and are not included in these databases. We have developed GWASdb that contains 20 times more data than the GWAS Catalog and includes less significant GVs (P < 1.0 × 10−3) manually curated from the literature. In addition, GWASdb provides comprehensive functional annotations for each GV, including genomic mapping information, regulatory effects (transcription factor binding sites, microRNA target sites and splicing sites), amino acid substitutions, evolution, gene expression and disease associations. Furthermore, GWASdb classifies these GVs according to diseases using Disease-Ontology Lite and Human Phenotype Ontology. It can conduct pathway enrichment and PPI network association analysis for these diseases. GWASdb provides an intuitive, multifunctional database for biologists and clinicians to explore GVs and their functional inferences. It is freely available at http://jjwanglab.org/gwasdb and will be updated frequently.

DNA methylation contributes to natural human variation

“…In this respect, DNA methylation might display a potent intermediate event that could be useful to interpret the GWAS results. For this reason, we performed model-based gene set analysis (Bauer et al 2011) to compare SNPs directly associated with popCpGs and GWA studies available at GWASdb (Li et al 2012). We found some interesting associations related to age of menarche, and HIV control; in particular, we determined highly significant enrichment for hepatitis B infection through the detection of six SNPs directly related to CpG sites that were differentially methylated between populations (Enrichment score: 0.99) (Supplemental Table S7; Bauer et al 2011).…”

“…To establish a causal relationship between genetic variability, DNA methylation level, and distinct phenotypes, we determined enrichment of meQTL-related SNPs in the entire set of GWA studies available at GWASdb (Li et al 2012) using model-based gene set analysis (Bauer et al 2011). The method analyzes all categories at once by embedding them in a Bayesian network.…”

Needles in the genetic haystack of lipid disorders: single nucleotide polymorphisms in the microRNA regulome

“…In the past few years, GWAS have been conducted for hundreds of complex diseases and traits ( 80 ). Several bioinformatic strategies have been developed to map GWAS-derived disease-associated variants, as well as SNPs in strong linkage disequilibrium (LD), onto predicted miRNA target sites (81)(82)(83)(84)(85)(86). A very recent approach uncovered 87 such SNPs ( 84 ).…”

Old Obstacles on New Horizons: The Challenge of Implementing Gene X Environment Discoveries in Schizophrenia Research

“…These contain a wealth of information highlighting the organisation, structure and function of the genome. Other specialist resources provide a dense functional annotation of regions that border GWAS hits (http://jjwanglab.org:8080/gwasdb/) 120 .…”