We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study.
- Authors
Wenming Wei; Huijie Zhang; Bolun Cheng; Xiaoyue Qin; Dan He; Na Zhang; Yijing Zhao; Qingqing Cai; Sirong Shi; Xiaoge Chu; Yan Wen; Huan Liu; Yumeng Jia; Feng Zhang
- Abstract
Objective. Genetic approaches are increasingly advantageous in characterizing treatmentresistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing bettertailored therapeutic targets. Methods. TRS-related proteome-wide association studies (PWAS) were conducted on genomewide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/- MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results. In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (PPWAS-ROS/MAP = 4.15 x 10-2 and PPWAS-Banner = 3.38 x 10-3 ) and APOL2 (PPWAS-ROS/MAP = 4.49 x 10-3 and PPWASBanner = 8.26 x 103 ). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions. Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role.
- Subjects
SCHIZOPHRENIA; LIPID peroxidation (Biology); PROTEINS; PROTEIN expression; FUNCTIONAL analysis; CONSORTIA; GENE ontology
- Publication
European Psychiatry, 2023, Vol 66, Issue 1, p1
- ISSN
0924-9338
- Publication type
Article
- DOI
10.1192/j.eurpsy.2023.20