ArticleJAMA psychiatry2025
Circulating Blood-Based Proteins in Psychopathology and Cognition: A Mendelian Randomization Study.
Article in JAMA psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- [Association between 473 gut microbiota and Alzheimer's disease: a Mendelian randomization mediation analysis of 233 circulating metabolites].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Schizophrenia: from mechanism to therapy.Science China. Life sciences · 2026Review
- Disorder-specific and shared genetic architecture underlying schizophrenia and bipolar disorder.medRxiv : the preprint server for health sciences · 2026Article
- Characterizing the impact of plasma protein levels on human brain structure and disorders leveraging integrative multi-omics analysis.medRxiv : the preprint server for health sciences · 2026Article
- Causal inference in psychiatric research: how to critically evaluate and interpret mendelian randomization studies.Molecular psychiatry · 2026Review
- Decreased serum IGFBP-7 level is associated with cognitive impairment in first-episode drug-naïve adolescent-onset schizophrenia.Annals of general psychiatry · 2026Article
- Genetic and Experimental Evidence Implicates CCL4 in Severe Sepsis Risk and Phase-Dependent Immune Dynamics.Journal of inflammation research · 2026Article
- Hepatic sEH drives stress-induced neuroinflammation via IL-6 and liver-brain axis.Frontiers in immunology · 2026Article
- A narrative review of recent literature of circulating biomarkers of abdominal aortic aneurysm.JVS-vascular science · 2026Review
- Delving into the Perception, Use, and Context of Duloxetine in Clinical Practice: An Analysis Based on the Experience of Healthcare Professionals.Brain sciences · 2025Article
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9 authors.
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Abstract
Importance: Peripheral (blood-based) biomarkers for psychiatric illness could benefit diagnosis and treatment, but research to date has typically been low throughput, and traditional case-control studies are subject to potential confounds of treatment and other exposures. Large-scale 2-sample mendelian randomization (MR) can examine the potentially causal impact of circulating proteins on neuropsychiatric phenotypes without these confounds. Objective: To identify circulating proteins associated with risk for schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) as well as cognitive task performance (CTP). Design, Setting, and Participants: In a 2-sample MR design, significant proteomic quantitative trait loci were used as candidate instruments, obtained from 2 large-scale plasma proteomics datasets: the UK Biobank Pharma Proteomics Project (2923 proteins per 34 557 UK individuals) and deCODE Genetics (4719 proteins per 35 559 Icelandic individuals). Data analysis was performed from November 2023 to November 2024. Exposure: Genetic influence on circulating levels of proteins in plasma. Main Outcomes and Measures: Outcome measures were summary statistics drawn from recent large-scale genome-wide association studies for SCZ (67 323 cases and 93 456 controls), BD (40 463 cases and 313 436 controls), MDD (166 773 cases and 507 679 controls), and CTP (215 333 individuals). MR was carried out for each phenotype, and proteins that showed statistically significant (Bonferroni-corrected P < .05) associations from MR analysis were used for pathway, protein-protein interaction, drug target enrichment, and potential druggability analysis for each outcome phenotype separately. Results: MR analysis revealed 113 Bonferroni-corrected associations (46 novel) involving 91 proteins across the 4 outcome phenotypes. Immune-related proteins, such as interleukins and complement factors, showed pleiotropic effects across multiple outcome phenotypes. Drug target enrichment analysis provided support for repurposing of anti-inflammatory agents for SCZ, amantadine for BD, retinoic acid for MDD, and duloxetine for CTP. Conclusions and Relevance: Identifying potentially causal effects of circulating proteins on neuropsychiatric phenotypes suggests potential biomarkers and offers insights for the development of innovative therapeutic strategies. The study also reveals pleiotropic effects of many proteins across different phenotypes, indicating shared etiology among serious psychiatric conditions and cognition.
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