Single-cell RNA sequencing identifies the specific cell types of GWAS genes associated with liver disease

Abstract Background The liver is an important digestive organ in the human body, which has a variety of physiological functions. Once the liver occurs dysfunction, it may indicate the occurrence of liver disease. Genome-wide association studies (GWAS) have identified a lot of genetic variants which are associated with liver disease. However, it is not clear that the genes with variants in which have cell type specificity. Methods To investigate the association between liver cell types and liver disease, we used a new method that integrate the genes associated with liver diseases identified by GWAS and single-cell RNA sequencing (scRNA-seq) data for analysis. We applied the scRNA-seq data from the GEO database, which included 20 cell types from human liver and 9 cell types from mouse liver after reclassifying. The susceptibility genes of liver diseases were downloaded from GWAS catalog and matched to the results of liver scRNA-seq. Results We found that most susceptibility genes of chronic hepatitis B virus (HBV) infection were expressed in human B cells. And the susceptibility genes of biomarkers of liver dysfunction showed similar cell type specificity in human and mouse. Last, we discovered that primary liver disease phenotypes may be due to mutations in multiple cell types. Conclusions Collectively, this study localized the susceptibility genes of liver diseases to specific cell types and provided clues for the in-depth study of liver diseases at the transcriptome level.