表达数量性状基因座
生物
孟德尔随机化
免疫系统
遗传学
全基因组关联研究
等位基因
电池类型
自身免疫性疾病
数量性状位点
外周血单个核细胞
疾病
孟德尔遗传
基因
遗传变异
细胞
单核苷酸多态性
遗传变异
基因型
抗体
医学
体外
病理
作者
Seyhan Yazar,José Alquicira-Hernández,Kristof Wing,Anne Senabouth,Mary Grace Gordon,Stacey B. Andersen,Qinyi Lu,Antonia C. Rowson,Thomas R. Taylor,Linda Clarke,Katia Maccora,Christine Chen,Anthony Cook,Chun Jimmie Ye,Kirsten A. Fairfax,Alex W. Hewitt,Joseph E. Powell
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2022-04-08
卷期号:376 (6589)
被引量:173
标识
DOI:10.1126/science.abf3041
摘要
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 naïve 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.
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