Chunk #50 — ONLINE METHODS — Data acquisition, quality control, and normalization — Enrichment of sQTLs within epigenomic marks and splicing factor binding sites.
We selected a set of 71 human curated RNA-binding proteins (RBP) splicing regulatory proteins from the SpliceAid-F database65 to analyze the relationship between gene expression levels of RBP and intron usage patterns across all samples. To test for enrichment of sQTLs in RBP binding sites, we downloaded human CLIP data in BED format from ClipDB34. We used GREGOR66 (Genomic Regulatory Elements and Gwas Overlap algoRithm) to evaluate global enrichment of trait-associated variants in splicing factor binding sites. GREGOR66 evaluates the significance of the observed overlap (of sQTL and splicing factor binding sites) by estimating the probability of the observed overlap of the lead sQTL relative to expectation using a set of matched control variants (random control SNPs are selected across the genome that match the index SNP for a number of variants in LD, minor allele frequency, and distance to nearest intron). We used Fisher’s Exact Test in combination with Benjamini-Hochberg False Discovery Rate (FDR) correction for multiple testing.
