Integrative Analysis of scRNA-seq and GWAS Data Pinpoints Periportal Hepatocytes as the Relevant Liver Cell Types for Blood Lipids.

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.