Integration of multi-omics summary data reveals the role of N6-methyladenosine in neuropsychiatric disorders.

N6-methyladenosine (m 6 A) 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 m 6 A in neuropsychiatric disorders by using transcriptome-wide association study (TWAS) tool and Summary-data-based Mendelian randomization (SMR). Our investigation identified 86 m 6 A sites associated with seven neuropsychiatric diseases and then revealed 7881 associations between m 6 A sites and gene expressions. Based on these results, we discovered 916 significant m 6 A-gene associations involving 82 disease-related m 6 A 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 m 6 A-disease, m 6 A-gene, and gene-disease for SCZ, BP, AD, MDD, and PD separately. Functional analysis showed the m 6 A mapped genes were enriched in "response to stimulus" pathway. In addition, we also analyzed the effect of gene expression on m 6 A and the post-transcription effect of m 6 A on protein. Our study provided new insights into the genetic component of m 6 A in neuropsychiatric disorders and unveiled potential pathogenic mechanisms where m 6 A exerts influences on disease through gene expression/protein regulation.