Tri-Institutional Program in Computational Biology & Medicine, Weill Cornell Medicine, New York, NY, USA.
Institute of Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
Nat Commun. 2020 May 5;11(1):2213. doi: 10.1038/s41467-020-16097-9.
Despite infiltrating immune cells having an essential function in human disease and patients' responses to treatments, mechanisms influencing variability in infiltration patterns remain unclear. Here, using bulk RNA-seq data from 46 tissues in the Genotype-Tissue Expression project, we apply cell-type deconvolution algorithms to evaluate the immune landscape across the healthy human body. We discover that 49 of 189 infiltration-related phenotypes are associated with either age or sex (FDR < 0.1). Genetic analyses further show that 31 infiltration-related phenotypes have genome-wide significant associations (iQTLs) (P < 5.0 × 10), with a significant enrichment of same-tissue expression quantitative trait loci in suggested iQTLs (P < 10). Furthermore, we find an association between helper T cell content in thyroid tissue and a COMMD3/DNAJC1 regulatory variant (P = 7.5 × 10), which is associated with thyroiditis in other cohorts. Together, our results identify key factors influencing inter-individual variability of immune infiltration, to provide insights on potential therapeutic targets.
尽管浸润免疫细胞在人类疾病和患者对治疗的反应中具有重要功能，但影响浸润模式变异性的机制仍不清楚。在这里，我们使用来自基因型-组织表达项目的 46 种组织的批量 RNA-seq 数据，应用细胞类型去卷积算法来评估整个健康人体的免疫景观。我们发现，189 种与浸润相关的表型中有 49 种与年龄或性别相关（FDR<0.1）。遗传分析进一步表明，31 种与浸润相关的表型具有全基因组显著关联（iQTLs）（P<5.0×10），在提示 iQTL 中存在相同组织表达数量性状基因座的显著富集（P<10）。此外，我们发现甲状腺组织中辅助性 T 细胞含量与 COMMD3/DNAJC1 调节变异体之间存在关联（P=7.5×10），该关联在其他队列中与甲状腺炎有关。总之，我们的研究结果确定了影响免疫浸润个体间变异性的关键因素，为潜在的治疗靶点提供了见解。
