Circulating Blood-Based Proteins in Psychopathology and Cognition

作者：Upasana Bhattacharyya, Jibin John, Max Lam, Jonah Fisher, Benjamin B. Sun, Denis Baird, Stephen Burgess, Chia‐Yen Chen, Todd Lencz · 发表于：JAMA Psychiatry · 年份：2025 · DOI：10.1001/jamapsychiatry.2025.0033 · 被引用次数：12 · 研究领域：Genetic Associations and Epidemiology、Tryptophan and brain disorders、Schizophrenia research and treatment

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 signif...