Large-Scale Mendelian Randomization Study Reveals Circulating Blood-based Proteomic Biomarkers for Psychopathology and Cognitive Task Performance
Bhattacharyya, U.; John, J.; Lam, M.; Fisher, J.; Sun, B.; Baird, D.; Chen, C.-Y.; Lencz, T.
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Research on peripheral (blood-based) biomarkers for psychiatric illness has typically been low-throughput, and traditional case-control studies are subject to potential confounds of treatment and other exposures. Here, we leverage large-scale, high-throughput proteomics data and Mendelian Randomization (MR) to examine the causal impact of circulating proteins on neuropsychiatric phenotypes. We utilized plasma proteomics data from the UK Biobank (3,072 proteins / 34,557 individuals) and deCODE Genetics (4,719 proteins / 35,559 individuals). Significant proteomic quantitative trait loci served as MR instruments, with the most recent GWAS for schizophrenia, bipolar disorder, major depressive disorder, and cognitive task performance as phenotypic outcomes. MR revealed 109 Bonferroni-corrected causal associations (44 novel) involving 88 proteins across the four phenotypes. Several immune-related proteins, including interleukins and complement factors, stood out as pleiotropic across multiple phenotypes. Identification of causal effects for these circulating proteins suggests potential biomarkers for these conditions and offers insights for developing innovative therapeutic strategies.
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