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

Rouhana, J. M.; Wang, J.; Eraslan, G.; Anand, S.; Hamel, A. R.; Cole, B.; Regev, A.; Aguet, F.; Ardlie, K. G.; Segre, A. V.

doi:10.1101/2021.11.24.469720

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bioRxiv · 10.1101/2021.11.24.469720

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

Rouhana, J. M.·Wang, J.·Eraslan, G.·Anand, S.·Hamel, A. R.·Cole, B.·Regev, A.·Aguet, F.·Ardlie, K. G.·Segre, A. V.

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Abstract

SummaryECLIPSER 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 Fishers 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 ImplementationThe 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.

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Rouhana, J. M., Wang, J., Eraslan, G., Anand, S., Hamel, A. R., Cole, B., Regev, A., Aguet, F., Ardlie, K. G., Segre, A. V.. 2021-11-25. ECLIPSER: identifying causal cell types and genes for complex traits through single cell enrichment of e/sQTL-mapped genes in GWAS loci. https://doi.org/10.1101/2021.11.24.469720

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