Protocol for identifying cell-type-specific genes associated with disease risk using single-cell eQTL data

Here, we present a protocol for mapping cell-type-specific cis -acting expression quantitative trait loci ( cis -eQTLs) in a target tissue and integrating them with genome-wide association study (GWAS) data. We describe pooled-sample multiplexed sequencing, genotype-based cell demultiplexing, cis -eQTL detection in specific cell types, and integration of single-cell eQTLs with GWAS. This protocol facilitates the identification of candidate risk genes and mechanisms underlying disease susceptibility. For complete details on the use and execution of this protocol, please refer to Bian et al. 1 • Multiplexed sequencing of pooled samples and genotype-based cell demultiplexing • Processing scRNA-seq data, identifying cell types, and mapping cis -eQTLs • Integrating cell-type-specific eQTL results with GWAS data • Linking regulatory variants to cell-type-specific regions using scATAC-seq data Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. Here, we present a protocol for mapping cell-type-specific cis -acting expression quantitative trait loci ( cis -eQTLs) in a target tissue and integrating them with genome-wide association study (GWAS) data. We describe pooled-sample multiplexed sequencing, genotype-based cell demultiplexing, cis -eQTL detection in specific cell types, and integration of single-cell eQTLs with GWAS. This protocol facilitates the identification of candidate risk genes and mechanisms underlying disease susceptibility.