SNP ratio test

SNP ratio test evaluates the enrichment of statistically significant single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) within predefined gene sets or pathways, such as KEGG and Gene Ontology (GO), to identify biological pathways associated with traits or diseases.

Key Features:

• Pathway contextual analysis: Examines the distribution of SNP associations across genes that are members of specific biological pathways.
• Ratio calculation: Computes the ratio of significant SNPs (meeting a predefined statistical threshold) to all SNPs within genes of interest for each pathway.
• Empirical P-value estimation: Compares observed SNP ratios to ratios from randomized datasets, where case and control statuses are shuffled, to derive empirical P-values.
• Database and user-defined pathway support: Applies to pathway definitions from KEGG and Gene Ontology (GO) and accepts user-defined pathway gene sets.

Scientific Applications:

• Pathway-level GWAS interpretation: Identifies pathways with non-random enrichment of significant SNPs to aid interpretation of GWAS results.
• Disease mechanism discovery: Detects pathways potentially implicated in disease susceptibility, exemplified by application to a Parkinson's disease GWAS using KEGG pathway annotations.

Methodology:

Assess SNP association distribution across pathway genes, calculate the ratio of significant SNPs to total SNPs per pathway (using a predefined significance threshold), and compare observed ratios to those from randomized case/control label shuffles to obtain empirical P-values.