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 forty cell types from human and mouse livers in order to construct the cell-type specifically expressed gene sets, which we refer to as CT-SEGS. Under the assumption that CT-SEGS represented specific functions of each cell type, we applied stratified linkage disequilibrium score regression (LDSC) to determine which cell types 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.

中文翻译：

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scRNA-seq 和 GWAS 数据的综合分析将门静脉周围肝细胞确定为血脂的相关肝细胞类型。

肝脏是一种由各种细胞类型组成的异质组织，已知与血脂特征相关。通过整合来自全基因组关联研究 (GWAS) 的脂质特征和肝脏单细胞转录组数据的汇总统计数据，我们试图确定肝脏中与血脂水平最相关的特定细胞类型。我们对来自人和小鼠肝脏的 40 种细胞类型进行了差异表达分析，以构建细胞类型特异性表达的基因集，我们将其称为 CT-SEGS。在 CT-SEGS 代表每种细胞类型的特定功能的假设下，我们应用分层连锁不平衡评分回归 (LDSC) 来确定哪些细胞类型与复杂性状和疾病最相关。我们首先通过识别与自身免疫疾病相关的免疫细胞类型来证实这种方法（描绘功能相关的细胞类型）的有效性。我们进一步表明脂质 GWAS 信号在人和小鼠门静脉周围肝细胞中富集。我们的结果提供了重要的信息，以促进影响血脂水平的代谢机制的未来细胞研究。