HaploReg

HaploReg annotates non-coding genetic variants and explores their regulatory and linkage context to prioritize candidate causal SNPs and indels for interpretation of GWAS and variant sets.

Key Features:

• LD mapping (1000 Genomes Project): Uses linkage disequilibrium information from the 1000 Genomes Project to identify and visualize SNPs and indels linked within haplotype blocks.
• Chromatin state annotations: Integrates chromatin state predictions across nine cell types to annotate regulatory elements.
• Conservation data: Includes conservation data across mammals to highlight evolutionarily constrained loci.
• Regulatory motif impact: Predicts potential impacts of variants on regulatory motifs.
• Candidate variant annotation: Annotates candidate regulatory single nucleotide polymorphisms (SNPs) and small insertions/deletions (indels), including intergenic variants, to aid causal variant selection.
• Enhancer enrichment analysis: Assesses enrichment of cell type-specific enhancers among SNP sets.

Scientific Applications:

• GWAS interpretation: Prioritizes and refines candidate causal variants from GWAS by accounting for linkage disequilibrium and regulatory annotations.
• Novel variant analysis: Annotates and analyzes novel SNP or indel sets to generate hypotheses about regulatory function.
• Cell type-specific inference: Identifies enrichment of cell type-specific enhancers to implicate relevant tissues or cell types.
• Mechanistic hypothesis generation: Supports development of mechanistic hypotheses linking non-coding variation to clinical phenotypes and normal biological variation.

Methodology:

Leverages LD information from the 1000 Genomes Project to visualize linked SNPs and indels and integrates chromatin state predictions across nine cell types, conservation data across mammals, and predicted impacts on regulatory motifs.