PICS2

PICS2 computes probabilistic causal assignments for single nucleotide polymorphisms (SNPs) in linkage disequilibrium with GWAS index SNPs to prioritize candidate causal variants for genetic studies.

Key Features:

• Batch processing capability: Processes large numbers of index SNPs in batch rather than one SNP at a time.
• Reference data utilization: Uses LD reference data from the 1000 Genomes phase 3 project for populations ALL, EUR, EAS, SAS, AFR, and AMR.
• Annotation features: Annotates variant consequences and GTEx eQTL genes and provides downloadable PICS probabilities for GTEx eQTLs.
• Integration with GWAS Catalog: Automatically updates weekly to generate PICS SNPs from all SNPs listed in the GWAS Catalog.
• Experimental summary statistics: Generates PICS probabilities using experimental summary statistics when provided.
• Causal likelihood assessment: Estimates the probability that each SNP in LD with a reported index SNP is the true causal variant using only index SNP information.

Scientific Applications:

• Candidate causal locus identification: Prioritizes potential causal SNPs underlying GWAS associations for downstream biological and functional follow-up.

Methodology:

Uses index SNPs from published GWAS and LD from 1000 Genomes phase 3 (ALL, EUR, EAS, SAS, AFR, AMR) to compute PICS probabilities estimating the likelihood that SNPs in LD with an index SNP are causal; can compute probabilities from experimental summary statistics and from GTEx eQTLs and updates SNP inputs from the GWAS Catalog weekly.