Combination of single cell sequencing data and GWAS summary statistics reveals genetically-influenced liver cell types for primary biliary cholangitis
Many genome-wide association studies (GWAS) have reported that numerous genetic loci were significantly associated with primary biliary cholangitis (PBC). However, the effects of genetic determinants on liver cells and its immune microenvironment for PBC remain unclear. We constructed a powerful computational framework to integrate a large-scale GWAS summary statistics (N = 13,239) with scRNA-seq data to uncover genetics-modulated liver cell subpopulations for PBC. We found that 29 genes including ORMDL3, GSNK2B, and DDAH2 were significantly associated with PBC susceptibility. Gene-property analysis revealed that four immune cell types including Cst3+ dendritic cell, Chil3+ macrophage, Trbc2+ T cell, and Gzma+ T cell were significantly enriched by PBC-risk genes. By combining GWAS summary statistics with scRNA-seq data, we identified that cholangiocytes exhibited a notable enrichment by PBC-related genetic association signals. The ORMDL3 gene showed the highest expression proportion in cholangiocytes than other liver cells (22.38%). Compared with ORMDL3+ cholangiocytes, we identified that ORMDL3- cholangiocytes predispose to play important immune-modulatory roles in the etiology of PBC. To the best of our knowledge, this is the first study to integrate human genetic information with single cell sequencing data for parsing genetics-influenced liver cells and its immune microenvironment for PBC risk.
- Downloaded 131 times
- Download rankings, all-time:
- Site-wide: 149,535
- In genetic and genomic medicine: 907
- Year to date:
- Site-wide: 71,145
- Since beginning of last month:
- Site-wide: 17,828
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!