Proteome-wide Mendelian randomization reveals the causal effects of immune-related plasma proteins on psychiatric disorders.

Abstract

Immune dysregulation has been consistently reported in psychiatric disorders, however, the causes and mechanisms underlying immune dysregulation in psychiatric disorders remain largely unclear. Here we conduct a Mendelian randomization study by integrating plasma proteome and GWASs of schizophrenia, bipolar disorder and depression. The primate-specific immune-related protein BTN3A3 showed the most significant associations with all three psychiatric disorders. In addition, other immune-related proteins, including AIF1, FOXO3, IRF3, CFHR4, IGLON5, FKBP2, and PI3, also showed significant associations with psychiatric disorders. Our study showed that a proportion of psychiatric risk variants may contribute to disease risk by regulating immune-related plasma proteins, providing direct evidence that connect the genetic risk of psychiatric disorders to immune system.

• Authors: Xinglun Dang, Meng Song, Luxian Lv, Yongfeng Yang, Xiong-Jian Luo
• Journal: Human genetics (Hum Genet) Vol. 142 Issue 6 Pg. 809-818 (Jun 2023) ISSN: 1432-1203 [Electronic] Germany
• PMID: 37085628 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Proteome
• Blood Proteins

Topics

• Animals
• Proteome (genetics, metabolism)
• Mendelian Randomization Analysis
• Mental Disorders (genetics)
• Bipolar Disorder (genetics)
• Blood Proteins
• Genome-Wide Association Study
• Polymorphism, Single Nucleotide