Liver, a heterogeneous tissue consisting of various cell types, is known to be relevant for blood lipid traits. By integrating summary statistics from genome-wide association studies (GWAS) of lipid traits and single-cell transcriptome data of the liver, we sought to identify specific cell types in the liver that were most relevant for blood lipid levels. We conducted differential expression analyses for 40 cell types from human and mouse livers in order to construct the cell-type specifically expressed gene sets, which we refer to as construction of the liver cell-type specifically expressed gene sets (CT-SEGS). Under the assumption that CT-SEGS represented specific functions of each cell type, we applied stratified linkage disequilibrium score regression to determine cell types that were most relevant for complex traits and diseases. We first confirmed the validity of this method (of delineating functionally relevant cell types) by identifying the immune cell types as relevant for autoimmune diseases. We further showed that lipid GWAS signals were enriched in the human and mouse periportal hepatocytes. Our results provide important information to facilitate future cellular studies of the metabolic mechanism affecting blood lipid levels.
基金:
National Natural Science Foundation of China (NSFC) [81973148, 82003561]
第一作者单位:[1]Huazhong Univ Sci & Technol, Dept Epidemiol & Biostat, Key Lab Environm & Hlth, Sch Publ Hlth, Wuhan 430030, Peoples R China[*1]Huazhong Univ Sci & Technol, Tongji Med Coll, 13 Hongkong Rd, Wuhan 430030, Hubei, Peoples R China
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol, Dept Epidemiol & Biostat, Key Lab Environm & Hlth, Sch Publ Hlth, Wuhan 430030, Peoples R China[*1]Huazhong Univ Sci & Technol, Tongji Med Coll, 13 Hongkong Rd, Wuhan 430030, Hubei, Peoples R China
推荐引用方式(GB/T 7714):
Hao Xingjie,Wang Kai,Dai Chengguqiu,et al.Integrative analysis of scRNA-seq and GWAS data pinpoints periportal hepatocytes as the relevant liver cell types for blood lipids[J].HUMAN MOLECULAR GENETICS.2020,29(18):3145-3153.doi:10.1093/hmg/ddaa188.
APA:
Hao, Xingjie,Wang, Kai,Dai, Chengguqiu,Ding, Zeyang,Yang, Wei...&Cheng, Shanshan.(2020).Integrative analysis of scRNA-seq and GWAS data pinpoints periportal hepatocytes as the relevant liver cell types for blood lipids.HUMAN MOLECULAR GENETICS,29,(18)
MLA:
Hao, Xingjie,et al."Integrative analysis of scRNA-seq and GWAS data pinpoints periportal hepatocytes as the relevant liver cell types for blood lipids".HUMAN MOLECULAR GENETICS 29..18(2020):3145-3153