Grünewald Lena, Chiocchetti Andreas G, Weber Heike, Scholz Claus-Jürgen, Schartner Christoph, Freudenberg Florian, Reif Andreas
University Hospital, Goethe University Frankfurt, Germany.
University Hospital Würzburg, Germany.
J Atten Disord. 2021 Feb;25(4):572-583. doi: 10.1177/1087054718822129. Epub 2019 Jan 9.
The gene is associated with ADHD, but its function is largely unknown. Thus, we aimed to explore the genes and molecular pathways affected by . Using short hairpin RNAs, we downregulated in murine hippocampal primary cells. Gene expression was analyzed by microarray and affected pathways were identified. We used quantitative real-time polymerase chain reaction (qPCR) to confirm expression changes and analyzed enrichment of differentially expressed genes in an ADHD GWAS (genome-wide association studies) sample. knockdown altered expression of 1,612 genes, which were enriched for biological processes involved in neurodevelopment. Expression changes were confirmed for 33 out of 88 selected genes. These 33 genes showed significant enrichment in ADHD patients in a gene-set-based analysis. Our findings show that affects numerous genes and thus molecular pathways that are relevant for neurodevelopmental processes. These findings may further support the hypothesis that is linked to etiological processes underlying ADHD.
该基因与注意力缺陷多动障碍（ADHD）相关，但其功能在很大程度上尚不清楚。因此，我们旨在探索受其影响的基因和分子途径。我们使用短发夹RNA在小鼠海马原代细胞中下调该基因。通过微阵列分析基因表达，并确定受影响的途径。我们使用定量实时聚合酶链反应（qPCR）来确认表达变化，并在ADHD全基因组关联研究（GWAS）样本中分析差异表达基因的富集情况。该基因的敲低改变了1612个基因的表达，这些基因在神经发育相关的生物学过程中富集。在88个选定基因中，有33个基因的表达变化得到了证实。在基于基因集的分析中，这33个基因在ADHD患者中显示出显著富集。我们的研究结果表明，该基因影响众多基因，进而影响与神经发育过程相关的分子途径。这些发现可能进一步支持该基因与ADHD潜在病因过程相关的假说。
