ArticleMolecular psychiatry2024
Genetic regulation of human brain proteome reveals proteins implicated in psychiatric disorders.
Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- Article
- Genome-wide fine-mapping improves identification of causal variants.Nature genetics · 2026Article
- Metabolic orchestration driven by GGCT: diverting glutamine to glutathione biosynthesis while enhancing glucose anaplerosis for tumor proliferation.Cell death & disease · 2026Article
- Human brain prefrontal cortex proteomics identifies compromised energy metabolism and neuronal function in Schizophrenia.Nature communications · 2026Article
- Genetic interaction ofFrontiers in neuroscience · 2026Article
- Similarities and differences between Alzheimer's disease and schizophrenia: drug target Mendelian randomization and transcriptome analysis.International journal of medical sciences · 2026Article
- Special Issue "Molecular Underpinnings of Schizophrenia Spectrum Disorders".International journal of molecular sciences · 2025Article
- Computational whole-body-exposome models for global precision brain health.Nature communications · 2025Article
- 5-HT6 receptors: Contemporary views on their neurobiological and pharmacological relevance in neuropsychiatric disorders.Dialogues in clinical neuroscience · 2025Review
- Impact of common variants on brain gene expression from RNA to protein to schizophrenia risk.Nature communications · 2025Article
- Inflammatory and Oxidative Biological Profiles in Mental Disorders: Perspectives on Diagnostics and Personalized Therapy.International journal of molecular sciences · 2025Review
- JUMPshiny: A User-Friendly Platform for Comprehensive Analysis and Visualization of Quantitative Proteomics Data.Proteomics · 2025Article
- MOADE: a multimodal autoencoder for dissociating bulk multi-omics data.Genome biology · 2025Article
- Efficient candidate drug target discovery through proteogenomics in a Scottish cohort.Communications biology · 2025Article
- Body fluid biomarkers and psychosis risk in The Accelerating Medicines Partnership® Schizophrenia Program: design considerations.Schizophrenia (Heidelberg, Germany) · 2025Article
- Genetic modulation of protein expression in rat brain.iScience · 2025Article
- Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes.Journal of neuroinflammation · 2024Article
- FMR1 genetically interacts with DISC1 to regulate glutamatergic synaptogenesis.Schizophrenia (Heidelberg, Germany) · 2024Article
- Promises and Challenges of populational Proteomics in Health and Disease.Molecular & cellular proteomics : MCP · 2024Article
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18 authors.
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Abstract
Psychiatric disorders are highly heritable yet polygenic, potentially involving hundreds of risk genes. Genome-wide association studies have identified hundreds of genomic susceptibility loci with susceptibility to psychiatric disorders; however, the contribution of these loci to the underlying psychopathology and etiology remains elusive. Here we generated deep human brain proteomics data by quantifying 11,608 proteins across 268 subjects using 11-plex tandem mass tag coupled with two-dimensional liquid chromatography-tandem mass spectrometry. Our analysis revealed 788 cis-acting protein quantitative trait loci associated with the expression of 883 proteins at a genome-wide false discovery rate <5%. In contrast to expression at the transcript level and complex diseases that are found to be mainly influenced by noncoding variants, we found protein expression level tends to be regulated by non-synonymous variants. We also provided evidence of 76 shared regulatory signals between gene expression and protein abundance. Mediation analysis revealed that for most (88%) of the colocalized genes, the expression levels of their corresponding proteins are regulated by cis-pQTLs via gene transcription. Using summary data-based Mendelian randomization analysis, we identified 4 proteins and 19 genes that are causally associated with schizophrenia. We further integrated multiple omics data with network analysis to prioritize candidate genes for schizophrenia risk loci. Collectively, our findings underscore the potential of proteome-wide linkage analysis in gaining mechanistic insights into the pathogenesis of psychiatric disorders.
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