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

作者：Dang X, Song M, Lv L, Yang Y, Luo XJ · 发表于：Human genetics · 年份：2023 · DOI：10.1007/s00439-023-02562-0

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.