研究人员展示了来自982名健康人的1,267,758个外周血单核细胞的单细胞RNA测序（scRNA-seq）数据。对于14种细胞类型，研究人员确定了26,597个独立的顺式eQTL和990个反式eQTL，其中大多数显示了细胞类型对基因表达的特异性影响。研究人员随后展示了eQTL如何在从初始状态过渡到记忆状态的B细胞中产生动态的等位基因效应，并证明常见的分离等位基因如何导致免疫功能的个体间差异。
最后，利用孟德尔随机化方法，研究人员确定了305个风险位点在细胞水平上对自身免疫性疾病的因果途径。这项工作将遗传流行病学与scRNA-seq结合起来，发现了免疫系统中个体间变异的驱动因素。
据悉，人类的免疫系统在个体之间显示出巨大的差异，导致对自身免疫性疾病的易感性不同。
附：英文原文
Title: Single-cell eQTL mapping identifies cell type–specific genetic control of autoimmune disease
Author: Seyhan Yazar, Jose Alquicira-Hernandez, Kristof Wing, Anne Senabouth, M. Grace Gordon, Stacey Andersen, Qinyi Lu, Antonia Rowson, Thomas R. P. Taylor, Linda Clarke, Katia Maccora, Christine Chen, Anthony L. Cook, Chun Jimmie Ye, Kirsten A. Fairfax, Alex W. Hewitt, Joseph E. Powell
Issue&Volume: 2022-04-08
Abstract: The human immune system displays substantial variation between individuals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type–specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from nave to memory states and demonstrate how commonly segregating alleles lead to interindividual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interindividual variation in the immune system.
DOI: abf3041
Source: https://www.science.org/doi/10.1126/science.abf3041