ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2023
Genome-wide Mendelian randomization identifies actionable novel drug targets for psychiatric disorders.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression.Nature human behaviour · 2025Pooled it
- The landscape of the methodology in drug repurposing using human genomic data: a systematic review.Briefings in bioinformatics · 2024Pooled it
- Molecular regulatory mechanisms of schizophrenia-associated functional non-coding variants.Molecular psychiatry · 2026Article
- Genome-wide pleiotropic analysis identifies shared genetic architecture within the cognition-immune nexus.Translational psychiatry · 2026Article
- An integrative mendelian randomisation and drug mechanism framework for target prioritisation and therapeutic repurposing in major depression.Translational psychiatry · 2026Article
- PSMB4/MHC-I Signaling in the Cerebrospinal Fluid-Contacting Nucleus Mediates Neuroinflammatory Depression in Mice.International journal of molecular sciences · 2026Article
- Multi-Omics Reveals Dysregulated Neurotransmitter Systems in Aging and CNS Disorders.Aging cell · 2026Article
- Lipid-lowering and glucose-lowering drug targets differentially modulate antipsychotic treatment efficacy in schizophrenia.Cell reports. Medicine · 2026Article
- Mapping spatially organized molecular and genetic signatures of schizophrenia across multiple scales in human prefrontal cortex.bioRxiv : the preprint server for biology · 2026Article
- Shared genetic architecture between schizophrenia and gastrointestinal diseases: insights from large-scale genome-wide cross-trait analysis.Annals of general psychiatry · 2026Article
- Proteome-wide Mendelian randomization and colocalization analyses identify potential biomarkers for schizophrenia.Frontiers in psychiatry · 2026Article
- Integrating Genetic and Single-Cell Genomic Data to Reveal Brain Cell-Specific Regulation of Attention-Deficit/Hyperactivity Disorder Risk in the Prefrontal Cortex.Brain and behavior · 2025Article
- Identification of Mood Disorders Causal Genes by Integrating the Brain Proteome and Transcriptome.Molecular neurobiology · 2025Article
- IMPDH2's Central Role in Cellular Growth and Diseases: A Potential Therapeutic Target.Cell proliferation · 2025Review
- Circulating Blood-Based Proteins in Psychopathology and Cognition: A Mendelian Randomization Study.JAMA psychiatry · 2025Article
- Cross-ancestry and sex-stratified genome-wide association analyses of amygdala and subnucleus volumes.Nature genetics · 2025Article
- Association of intestinal anti-inflammatory drug target genes with psychiatric Disorders: A Mendelian randomization study.Journal of advanced research · 2025Article
- Implications of gene × environment interactions in post-traumatic stress disorder risk and treatment.The Journal of clinical investigation · 2025Review
- PSMB4: a potential biomarker and therapeutic target for depression, perspective from integration analysis of depression GWAS data and human plasma proteome.Translational psychiatry · 2025Article
- Linking Genome-Wide Association Studies to Pharmacological Treatments for Psychiatric Disorders.JAMA psychiatry · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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