Single-cell eQTL mapping reveals cell-type-specific genetic regulation in lung cancer

作者：Yating Fu, Yi Wang, Chen Jin, Chang Zhang, Jiaying Cai, Linnan Gong, Chenying Jin, Gang Chen, Yuanlin Mou, Caochen Zhang, Shihao Wu, Xinyuan Ge, Yahui Dai, Sunan Miao, Huimin Ma, Xiaoyang Ma, Xiaoyang Ma, Mengping Wang, Lijun Bian, Erbao Zhang, Juncheng Dai, Zhibin Hu, Guangfu Jin, Meng Zhu, Hongbing Shen, Hongxia Ma, Hongxia Ma · 发表于：Cell Genomics · 年份：2025 · DOI：10.1016/j.xgen.2025.101100 · 被引用次数：4 · 研究领域：Single-cell and spatial transcriptomics、Genetic Associations and Epidemiology、Ferroptosis and cancer prognosis

Genome-wide association studies (GWASs) have identified over 50 lung cancer risk loci; however, the precise cellular context of these genetic mechanisms remains unclear due to limitations in bulk tissue expression quantitative trait locus (eQTL) analyses. Here, we present the largest single-cell eQTL (sc-eQTL) atlas of human lung tissue to date, profiling 222 donors using multiplexed single-cell RNA sequencing (scRNA-seq). We identified 4,341 independent eQTLs across 17 cell types, with over 60% of sc-eQTLs and 51% of eGenes being cell-type specific, and fewer than 52% were detectable in paired bulk datasets. Integration with GWASs for non-small cell lung cancer highlighted epithelial and immune cells as key contributors to genetic susceptibility, identifying 28 candidate genes within known risk loci and 24 in novel regions. Notably, 47% of established non-small cell lung cancer (NSCLC) susceptibility loci exhibited cell-type-specific pleiotropic genetic regulation. This study provides a valuable resource of lung sc-eQTLs and illuminates how genetic variation modulates gene expression in a cell-type-specific fashion, contributing to lung cancer susceptibility.