ArticlePLoS genetics2021
Identifying drug targets for neurological and psychiatric disease via genetics and the brain transcriptome.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 3 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Summarizing attributable factors and evaluating risk of bias of Mendelian randomization studies for Alzheimer's dementia and cognitive status: a systematic review and meta-analysis.Systematic reviews · 2025Pooled it
- Mendelian randomization and genetic colocalization infer the effects of the multi-tissue proteome on 211 complex disease-related phenotypes.Genome medicine · 2022Pooled it
- Guidelines for bioinformatics of single-cell sequencing data analysis in Alzheimer's disease: review, recommendation, implementation and application.Molecular neurodegeneration · 2022Pooled it
- Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization.PLoS computational biology · 2026Article
- Precision medicine in mental health: applications, challenges, and recommendations.European psychiatry : the journal of the Association of European Psychiatrists · 2026Review
- Repurposing drugs for the prevention of vascular dementia using evidence from drug target Mendelian randomization.Nature aging · 2026Article
- Network pharmacology-based discovery and experimental validation of novel drug repurposing candidates in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Network pharmacology approach to unravel the neuroprotective potential of natural products: a narrative review.Molecular diversity · 2026Review
- Functional variants at 1p36.23 confer risk of schizophrenia through modulating RERE.Nature communications · 2026Article
- Transcriptome-wide Mendelian randomization and single-cell analysis during CD4NPJ precision oncology · 2025Article
- Can classical statistics and deep learning converge on explainable, causally driven target discovery?DNA research : an international journal for rapid publication of reports on genes and genomes · 2025Review
- Mendelian randomization identifies proteins involved in neurodegenerative diseases.Brain : a journal of neurology · 2025Article
- Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes.Nature genetics · 2025Article
- Linking Genome-Wide Association Studies to Pharmacological Treatments for Psychiatric Disorders.JAMA psychiatry · 2025Article
- Leveraging pleiotropy for the improved treatment of psychiatric disorders.Molecular psychiatry · 2025Review
- Molecular pathogenesis of Alzheimer's disease onset in a mouse model: effects of cannabidiol treatment.Frontiers in neuroscience · 2025Article
- Potential Functions and Causal Associations of GNLY in Primary Open-Angle Glaucoma: Integration of Blood-Derived Proteome, Transcriptome, and Experimental Verification.Journal of inflammation research · 2025Article
- Identification of novel risk genes for Alzheimer's disease by integrating genetics from hippocampus.Scientific reports · 2024Article
- Progress and Implications from Genetic Studies of Bipolar Disorder.Neuroscience bulletin · 2024Review
- Optimising the use of electronic medical records for large scale research in psychiatry.Translational psychiatry · 2024Review
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
Discovering drugs that efficiently treat brain diseases has been challenging. Genetic variants that modulate the expression of potential drug targets can be utilized to assess the efficacy of therapeutic interventions. We therefore employed Mendelian Randomization (MR) on gene expression measured in brain tissue to identify drug targets involved in neurological and psychiatric diseases. We conducted a two-sample MR using cis-acting brain-derived expression quantitative trait loci (eQTLs) from the Accelerating Medicines Partnership for Alzheimer's Disease consortium (AMP-AD) and the CommonMind Consortium (CMC) meta-analysis study (n = 1,286) as genetic instruments to predict the effects of 7,137 genes on 12 neurological and psychiatric disorders. We conducted Bayesian colocalization analysis on the top MR findings (using P<6x10-7 as evidence threshold, Bonferroni-corrected for 80,557 MR tests) to confirm sharing of the same causal variants between gene expression and trait in each genomic region. We then intersected the colocalized genes with known monogenic disease genes recorded in Online Mendelian Inheritance in Man (OMIM) and with genes annotated as drug targets in the Open Targets platform to identify promising drug targets. 80 eQTLs showed MR evidence of a causal effect, from which we prioritised 47 genes based on colocalization with the trait. We causally linked the expression of 23 genes with schizophrenia and a single gene each with anorexia, bipolar disorder and major depressive disorder within the psychiatric diseases and 9 genes with Alzheimer's disease, 6 genes with Parkinson's disease, 4 genes with multiple sclerosis and two genes with amyotrophic lateral sclerosis within the neurological diseases we tested. From these we identified five genes (ACE, GPNMB, KCNQ5, RERE and SUOX) as attractive drug targets that may warrant follow-up in functional studies and clinical trials, demonstrating the value of this study design for discovering drug targets in neuropsychiatric diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.