Genome-wide Mendelian randomization identifies actionable novel drug targets for psychiatric disorders

	Genome-wide Mendelian randomization identifies actionable novel drug targets for psychiatric disorders
	Liu, JW; Cheng, YQ; Li, M; Zhang, ZJ; Li, T; Luo, XJ
	2023
发表期刊	NEUROPSYCHOPHARMACOLOGY
ISSN	0893-133X
卷号	48 期号:2 页码:270-280
摘要	Psychiatric disorders impose tremendous economic burden on society and are leading causes of disability worldwide. However, only limited drugs are available for psychiatric disorders and the efficacy of most currently used drugs is poor for many patients. To identify novel therapeutic targets for psychiatric disorders, we performed genome-wide Mendelian randomization analyses by integrating brain-derived molecular quantitative trait loci (mRNA expression and protein abundance quantitative trait loci) of 1263 actionable proteins (targeted by approved drugs or drugs in clinical phase of development) and genetic findings from large-scale genome-wide association studies (GWASs). Using transcriptome data, we identified 25 potential drug targets for psychiatric disorders, including 12 genes for schizophrenia, 7 for bipolar disorder, 7 for depression, and 1 (TIE1) for attention deficit and hyperactivity. We also identified 10 actionable drug targets by using brain proteome data, including 4 (HLA-DRB1, CAMKK2, P2RX7, and MAPK3) for schizophrenia, 1 (PRKCB) for bipolar disorder, 6 (PSMB4, IMPDH2, SERPINC1, GRIA1, P2RX7 and TAOK3) for depression. Of note, MAPK3 and HLA-DRB1 were supported by both transcriptome and proteome-wide MR analyses, suggesting that these two proteins are promising therapeutic targets for schizophrenia. Our study shows the power of integrating large-scale GWAS findings and transcriptomic and proteomic data in identifying actionable drug targets. Besides, our findings prioritize actionable novel drug targets for development of new therapeutics and provide critical drug-repurposing opportunities for psychiatric disorders.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13345
专题	科研部门_神经系统疾病（罗雄剑）
推荐引用方式 GB/T 7714	Liu, JW,Cheng, YQ,Li, M,et al. Genome-wide Mendelian randomization identifies actionable novel drug targets for psychiatric disorders[J]. NEUROPSYCHOPHARMACOLOGY,2023,48(2):270-280.
APA	Liu, JW,Cheng, YQ,Li, M,Zhang, ZJ,Li, T,&Luo, XJ.(2023).Genome-wide Mendelian randomization identifies actionable novel drug targets for psychiatric disorders.NEUROPSYCHOPHARMACOLOGY,48(2),270-280.
MLA	Liu, JW,et al."Genome-wide Mendelian randomization identifies actionable novel drug targets for psychiatric disorders".NEUROPSYCHOPHARMACOLOGY 48.2(2023):270-280.

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