Identification of novel proteins associated with movement-related adverse antipsychotic effects by integrating GWAS data and human brain proteomes

全基因组关联研究 候选基因 生物 孟德尔随机化 遗传关联 计算生物学 神经科学 遗传学 基因 单核苷酸多态性 基因型 遗传变异
作者
Jiqing Li,Jicheng Pang,Shucheng Si,Kai Zhang,Fang Tang,Fuzhong Xue
出处
期刊:Psychiatry Research-neuroimaging [Elsevier BV]
卷期号:317: 114791-114791 被引量:3
标识
DOI:10.1016/j.psychres.2022.114791
摘要

Genome-wide association studies (GWAS) have identified some variants for movement-related adverse antipsychotic effects (MAAE), while how these variants confer MAAE remains unclear. We used the probabilistic Mendelian randomization (PMR) method to identify candidate proteins for MAAE by integrating MAAE GWASs and protein quantitative trait loci (pQTL) data. An independent pQTL data from the Banner project and brain-derived eQTL data were used to perform confirmatory PMR. A total of 56 proteins were identified as candidate targets for MAAE after false discovery rates (FDR) correction, such as GRIN2B, ADRA1A, and PED4B. 12 genes were replicated in the confirmatory PMR, and 18 genes had consistent evidence at the transcript level. Furthermore, we investigated the associations between candidate proteins and the motor symptoms of Parkinson's disease (PD). There were 24, 38, and 10 candidate proteins that were significantly associated with PD, PD motor subtypes, and PD motor progression, respectively. Enrichment analysis identified 34 GO terms and 17 pathways that may be involved in MAAE, such as glutamatergic synapse, glutamate receptor complex, and GABAergic synapse. Our study identified multiple candidate genes and pathways that were associated with MAAE, providing new insights into the biological mechanism of MAAE and targets for further mechanistic and therapeutic studies.
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