ECLIPSER: identifying causal cell types and genes for complex traits through single cell enrichment of e/sQTL-mapped genes in GWAS loci

Summary ECLIPSER was developed to identify pathogenic cell types and cell type-specific genes that may affect complex disease susceptibility and trait variation by integrating single cell data with known GWAS loci. ECLIPSER maps genes to GWAS loci for a given complex trait based on expression and splicing quantitative trait loci (e/sQTLs) and other functional data, and tests whether the mapped genes are enriched for cell type-specific expression in particular cell types using single-cell/nucleus RNA-seq data from one or more tissues of interest. A Bayesian Fisher’s exact test is used to compute fold-enrichment significance. We demonstrate the application of ECLIPSER on various skin diseases and traits using snRNA-seq of healthy human skin samples. Availability and Implementation The source code and documentation for ECLIPSER and a Jupyter notebook for generating output tables and figures are available at https://github.com/segrelabgenomics/ECLIPSER . The source code for GWASvar2gene that maps genes to GWAS loci based on e/sQTLs is available at https://github.com/segrelabgenomics/GWASvar2gene . The analysis presented here used data from GTEx ( https://gtexportal.org/home/datasets ) and Open Targets Genetics ( https://genetics-docs.opentargets.org/data-access/graphql-api ), but can also be applied to other GWAS variant lists and QTL studies. Data used to reproduce the results of the paper are available in Supplementary data.