Department of Clinical Sciences and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
ISGlobal, Institute for Global Health, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Environ Int. 2021 Jan;146:106248. doi: 10.1016/j.envint.2020.106248. Epub 2020 Nov 16.
Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 µm in diameter (PM) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM exposure.
空气污染与整个生命过程中的健康不良影响有关。尽管潜在机制尚不清楚，但有几项研究表明，污染物会引起转录组谱的变化。在这项对三个参与 MeDALL 联盟的欧洲队列中的 656 名儿童和青少年进行的全转录组关联研究的荟萃分析中，我们发现了两个与出生时暴露于直径小于 2.5 µm 的颗粒物（PM）相关的差异表达转录簇（FDR p<0.05），其中一个映射到 MIR1296 基因。此外，我们通过使用功能表观遗传模块算法将基因表达与 DNA 甲基化相结合，发现了与出生时和当前住址的 PM 暴露相关的 9 个和 6 个模块（包括 NR1I2、MAPK6、TAF8 和 SCARA3）。总之，出生时的 PM 暴露与儿童和青少年的差异基因表达有关。重要的是，我们确定了与 PM 暴露相关的几个与复杂疾病相关的基因模块的重要互作热点。
