SpecVar

SpecVar leverages context-specific regulatory networks to associate single nucleotide polymorphisms (SNPs) with regulatory elements and perform heritability enrichment analyses using GWAS summary statistics.

Key Features:

• Multi-omics integration: Integrates chromatin accessibility and gene expression data to construct context-specific regulatory networks.
• Context-specific regulatory network atlas: Builds a detailed regulatory network atlas tailored to specific cellular contexts.
• SNP-to-regulatory-element association: Associates SNPs with context-specific regulatory elements to link genetic variants to regulatory mechanisms.
• Heritability enrichment analysis: Uses GWAS summary statistics to quantify heritability enrichment within context-specific regulatory annotations.
• Tissue relevance prioritization: Prioritizes phenotype-relevant tissues by assessing SNP enrichment in tissue-specific regulatory elements.
• Relevance correlation estimation: Estimates relevance correlations to depict common genetic factors across shared regulatory networks between traits.
• Validation and benchmarking: Demonstrates performance via ablation studies, independent data validation, and comparative experiments on GWAS data from six phenotypes.
• Large-scale phenotype analysis: Applied to 206 phenotypes from the UK Biobank to prioritize relevant tissues and shared heritability.

Scientific Applications:

• Complex trait interpretation: Dissects the regulatory basis of complex traits by linking SNPs to context-specific regulatory networks and heritability enrichment.
• Tissue identification: Identifies and prioritizes tissues relevant to specific phenotypes based on SNP-regulatory element associations.
• Causal regulation prioritization: Prioritizes gene regulatory mechanisms underlying trait-associated SNPs.
• Shared heritability and cross-trait analysis: Reveals shared SNP-associated regulations and common genetic factors between phenotype pairs.
• Population-scale phenotype prioritization: Enables large-scale prioritization of phenotype-relevant tissues across UK Biobank phenotypes.

Methodology:

Integrates chromatin accessibility and gene expression to form context-specific regulatory networks; associates SNPs with context-specific regulatory elements; performs heritability enrichment analysis using GWAS summary statistics; estimates relevance correlation across networks to depict shared genetic factors.