GenoWAP

GenoWAP integrates genomic functional annotation with GWAS test statistics to prioritize loci and distinguish likely functional variants in genome-wide association studies.

Key Features:

• Annotation integration: Combines genomic functional annotation with GWAS test statistics to inform variant and locus prioritization.
• Locus prioritization: Ranks loci to improve detectability of disease-associated signals that may be missed by genome-wide significance alone.
• Bonferroni-aware analysis: Addresses conservative Bonferroni-corrected significance levels that reduce statistical power for moderate-effect risk loci.
• LD and haplotype handling: Accounts for linkage disequilibrium (LD) structures and large haplotype blocks to help distinguish causal variants from correlated nonfunctional variants.
• Replication enhancement: Aims to increase signal replication rates across datasets through prioritized ranking.
• SNP-level ranking and eQTL enrichment: Produces single nucleotide polymorphism (SNP) rankings where top-ranked SNPs show higher replication rates and enrichment for expression quantitative trait loci (eQTLs).
• Subset-based prioritization: Can prioritize loci using GWAS results from a subset of samples to yield stronger signals when evaluated on the full dataset.

Scientific Applications:

• Crohn's disease GWAS: Applied to large-scale Crohn's disease studies to prioritize loci and improve replication of signals.
• Schizophrenia GWAS: Applied to schizophrenia datasets to prioritize loci and distinguish functional sites within correlated SNP groups.
• Fine-mapping of risk loci: Supports identification of likely functional variants within associated loci for downstream experimental follow-up.
• Replication and eQTL enrichment analyses: Facilitates evaluation of replication rates and enrichment of prioritized variants for eQTLs.

Methodology:

Leverages genomic functional annotations alongside GWAS test statistics to prioritize loci and identify potential functional sites among correlated markers, with prioritization demonstrably improving replication when based on a subset of samples.