Abstract
Background Anxiety disorder is a common mental disorder,with its prevalence showing a continuous upward trend,significantly affecting the quality of life and social function of patients.Due to the lack of objective and reliable biomarkers in clinical practice,the early identification and treatment of anxiety disorder have been somewhat limited.Plasma proteins have the potential to serve as biomarkers for mental diseases,however,the causal relationship between them and anxiety disorder remains unclear.Objective To identify the plasma proteins that have a causal relationship with anxiety disorders,and to elucidate the associated biological pathways,in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets.Methods Based on the protein quantitative trait locus(pQTL)data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database,and the genome-wide association studies(GWAS)data of 50 486 patients with anxiety disorders and 330 460 healthy controls,the inverse-variance weighted(IVW)method was used as the main analysis method,supplemented by MR-Egger method,weighted median method,simple model method,and weighted model method for bidirectional Mendelian randomization analysis.Enrichment analysis of gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways was conducted for the related proteins.Sensitivity analysis was performed using Cochran's Q test,MR-Egger intercept test,MR-PRESSO test,and leave-one-out analysis to evaluate the robustness of the results.Results A total of 10 plasma proteins were identified as significantly associated with anxiety disorders.Among these,SPATA9(OR=0.856,95%CI:0.784-0.934,P<0.01)and PDE5A(OR=0.911,95%CI:0.864-0.961,P<0.01)were identified as protective factors,while CRYGD(OR=1.209,95%CI:1.095-1.334,P<0.01),BTN3A3(OR=1.045,95%CI:1.018-1.073,P<0.01),SERPINB13(OR=1.102,95%CI:1.040-1.168,P<0.01),ERBB4(OR=1.283,95%CI:1.109-1.484,P<0.01),LSAMP(OR=1.096,95%CI:1.037-1.158,P<0.01),ICOSLG(OR=1.283,95%CI:1.104-1.490,P<0.01),DNAJB11(OR=1.172,95%CI:1.076-1.277,P<0.01),and TREML1(OR=1.115,95%CI:1.054-1.179,P<0.01)were identified as risk factors.The sensitivity analysis showed that the results were robust,with no heterogeneity(Cochran's Q test P>0.05)or pleiotropy(MR-Egger intercept test P>0.05).Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction,lymphocyte proliferation,cell membrane structure and synaptic function,as well as the intestinal immune network that produces IgA and the ErbB signaling pathway.Conclusion This study identified 10 plasma proteins associated with anxiety disorders.The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.关键词
焦虑障碍/血浆蛋白/孟德尔随机化/生物标志物Key words
Anxiety disorders/Plasma proteins/Mendelian randomization/Biomarkers分类
医药卫生
