N6-methyladenosine (m⁶A) methylation regulates gene expression/protein by influencing numerous aspects of mRNA metabolism and contributes to neuropsychiatric diseases. Here, we integrated multi-omics data and genome-wide association study summary data of schizophrenia (SCZ), bipolar disorder (BP), attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), major depressive disorder (MDD), Alzheimer’s disease (AD), and Parkinson’s disease (PD) to reveal the role of m⁶A in neuropsychiatric disorders by using transcriptome-wide association study (TWAS) tool and Summary-data-based Mendelian randomization (SMR). Our investigation identified 86 m⁶A sites associated with seven neuropsychiatric diseases and then revealed 7881 associations between m⁶A sites and gene expressions. Based on these results, we discovered 916 significant m⁶A–gene associations involving 82 disease-related m⁶A sites and 606 genes. Further integrating the 58 disease-related genes from TWAS and SMR analysis, we obtained 61, 8, 7, 3, and 2 associations linking m⁶A-disease, m⁶A–gene, and gene-disease for SCZ, BP, AD, MDD, and PD separately. Functional analysis showed the m⁶A mapped genes were enriched in “response to stimulus” pathway. In addition, we also analyzed the effect of gene expression on m⁶A and the post-transcription effect of m⁶A on protein. Our study provided new insights into the genetic component of m⁶A in neuropsychiatric disorders and unveiled potential pathogenic mechanisms where m⁶A exerts influences on disease through gene expression/protein regulation.

N6-甲基腺苷 (m ⁶ A) 甲基化通过影响 mRNA 代谢的多个方面来调节基因表达/蛋白质，并导致神经精神疾病。在这里，我们整合了精神分裂症（SCZ）、双相情感障碍（BP）、注意缺陷多动障碍（ADHD）、自闭症谱系障碍（ASD）、重度抑郁症（MDD）的多组学数据和全基因组关联研究汇总数据，阿尔茨海默病 (AD) 和帕金森病 (PD)通过使用全转录组关联研究 (TWAS) 工具和基于摘要数据的孟德尔随机化 (SMR)揭示 m ⁶ A 在神经精神疾病中的作用。我们的研究确定了与七种神经精神疾病相关的 86 m ⁶ A 位点，然后揭示了 m ⁶ A 位点与基因表达之间的 7881 个关联。基于这些结果，我们发现了 916 个显着的 m ⁶ A 基因关联，涉及 82 个与疾病相关的 m ⁶ A 位点和 606 个基因。进一步整合来自 TWAS 和 SMR 分析的 58 个疾病相关基因，我们获得了 m ⁶ A 疾病、m ⁶ A 基因和 SCZ、BP、AD 基因疾病之间的 61、8、7、3 和 2 个关联、MDD 和 PD 分别。功能分析显示 m ⁶ A 定位基因在“刺激反应”途径中富集。此外，我们还分析了基因表达对m ^{6 A的影响以及m 6} A对蛋白质的转录后影响。我们的研究为 m ⁶ A 在神经精神疾病中的遗传成分提供了新的见解，并揭示了 m ⁶ A 通过基因表达/蛋白质调节对疾病产生影响的潜在致病机制。