This Web site presents variants and loci associated in GWAS studies listed below, in the context of genomic regulatory blocks (GRBs). The aim here is to provide, in case where a disease-assocated locus is found overlapping a GRB, a comprehensive view of the range of conserved synteny around the locus. In the case where causative non-coding SNP within that locus is suspected to not have a local effect, i.e. the SNP is disrupting a regulatory element affecting a gene over a large distance, GRB model provides
Currently this app covers variants detected as genome-wide significant in the 2014. PGC GWAS study. LD blocks=loci
Genomic regulatory blocks have been called between human (hg19) and mouse (mm10) and the full set of these GRBs with target genes can be found here. Watch this space or contact our group (b dot lenhard at lms.mrc.ac.uk) in case you need an up to date set of GRBs, and please make sure to consider using other evolutionary distances depending on the trait being analysed.
There are several levels on which one can start looking into variants involved in long-range regulation. “All SNPs” provides all SNPs in a chosen study in a tabular form summarising SNP and LD block information from the original paper, and in case where SNP is in a locus that overlaps a GRB, all genes within that GRB are listed and classified either as targets or bystanders (more distant Metazoa for more ancient phenotypes).
“All loci”, like all SNPs provide information on all loci in a chosen GWAS study in a tabular form. The user is encouraged to focus on subset of SNPs/loci that fall within GRBs only, as there is no additional information we can provide for the ones outside of GRBs. Clicking on the individual entry under “locusPosition” will lead to per-locus summary page, see below.
“Locus summary” page provides additional information for a locus overlapping a GRB, like the list of the GRB target and bystander genes.
In the case where the locus is found to contain at least one permissive enhancer from FANTOM5, this page will contain two additional Figures linking these enhancers to all GWAS- and GRB-associated promoters in the region. First, a schema of the genomic region encompassing the GWAS locus and the GRB is presented:
Here is an example of a the DRD2 locus and the GRB pointing to another target, NCAM1, also significantly activated by the enhancer driving the expression of the DRD2:
The loci from the Pardinas et al. (2018.) study have been analysed in the same way and the plots can be found here: genomic neighbourhood and enhancer-promoter associations.