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• W4306405557 abstract "Abstract Background The rapid accumulation of single-cell RNA sequencing (scRNA-seq) data presents unique opportunities to decode the genetically mediated cell-type specificity in complex diseases. Here, we develop a new method, scGWAS, which effectively leverages scRNA-seq data to achieve two goals: (1) to infer the cell types in which the disease-associated genes manifest and (2) to construct cellular modules which imply disease-specific activation of different processes. Results scGWAS only utilizes the average gene expression for each cell type followed by virtual search processes to construct the null distributions of module scores, making it scalable to large scRNA-seq datasets. We demonstrated scGWAS in 40 genome-wide association studies (GWAS) datasets (average sample size N ≈ 154,000) using 18 scRNA-seq datasets from nine major human/mouse tissues (totaling 1.08 million cells) and identified 2533 trait and cell-type associations, each with significant modules for further investigation. The module genes were validated using disease or clinically annotated references from ClinVar, OMIM, and pLI variants. Conclusions We showed that the trait-cell type associations identified by scGWAS, while generally constrained to trait-tissue associations, could recapitulate many well-studied relationships and also reveal novel relationships, providing insights into the unsolved trait-tissue associations. Moreover, in each specific cell type, the associations with different traits were often mediated by different sets of risk genes, implying disease-specific activation of driving processes. In summary, scGWAS is a powerful tool for exploring the genetic basis of complex diseases at the cell type level using single-cell expression data." @default.
• W4306405557 created "2022-10-17" @default.
• W4306405557 creator A5006688612 @default.
• W4306405557 creator A5014283519 @default.
• W4306405557 creator A5024306478 @default.
• W4306405557 creator A5043473632 @default.
• W4306405557 creator A5056121087 @default.
• W4306405557 date "2022-10-17" @default.
• W4306405557 modified "2023-10-05" @default.
• W4306405557 title "scGWAS: landscape of trait-cell type associations by integrating single-cell transcriptomics-wide and genome-wide association studies" @default.
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