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Integrative analysis of scRNA-seq and GWAS data pinpoints periportal hepatocytes as the relevant liver cell types for blood lipids

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单位: [1]Huazhong Univ Sci & Technol, Dept Epidemiol & Biostat, Key Lab Environm & Hlth, Sch Publ Hlth, Wuhan 430030, Peoples R China [2]Huazhong Univ Sci & Technol,Hepat Surg Ctr,Tongji Hosp,Wuhan 430030,Peoples R China [3]Huazhong Univ Sci & Technol, Dept Nutr & Food Hyg, Sch Publ Hlth, Wuhan 430030, Peoples R China [4]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Orthoped Surg,Wuhan 430030,Peoples R China
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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.

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出版当年[2019]版:
大类 | 2 区 生物
小类 | 2 区 生化与分子生物学 2 区 遗传学
最新[2025]版:
大类 | 2 区 生物学
小类 | 3 区 生化与分子生物学 3 区 遗传学
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出版当年[2018]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 GENETICS & HEREDITY
最新[2023]版:
Q2 GENETICS & HEREDITY Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

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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
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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
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