HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants

TLDR

Genome‑wide association studies are limited by population linkage disequilibrium, making causal variant identification straightforward in coding regions but difficult in intergenic areas, though recent conservation and epigenomic data help predict functional non‑coding sequences. HaploReg is a tool for exploring non‑coding genome annotations in published GWAS results or novel variant sets. It uses 1000 Genomes linkage data to display linked SNPs and indels with predicted chromatin states in nine cell types, cross‑species conservation, and regulatory motif effects, and evaluates SNP sets for enrichment of cell‑type‑specific enhancers. HaploReg aids researchers in generating mechanistic hypotheses about non‑coding variant impacts on phenotypes and is available at http://compbio.mit.edu/HaploReg.

Abstract

The resolution of genome-wide association studies (GWAS) is limited by the linkage disequilibrium (LD) structure of the population being studied. Selecting the most likely causal variants within an LD block is relatively straightforward within coding sequence, but is more difficult when all variants are intergenic. Predicting functional non-coding sequence has been recently facilitated by the availability of conservation and epigenomic information. We present HaploReg, a tool for exploring annotations of the non-coding genome among the results of published GWAS or novel sets of variants. Using LD information from the 1000 Genomes Project, linked SNPs and small indels can be visualized along with their predicted chromatin state in nine cell types, conservation across mammals and their effect on regulatory motifs. Sets of SNPs, such as those resulting from GWAS, are analyzed for an enrichment of cell type-specific enhancers. HaploReg will be useful to researchers developing mechanistic hypotheses of the impact of non-coding variants on clinical phenotypes and normal variation. The HaploReg database is available at http://compbio.mit.edu/HaploReg.