Differential Association of the DISC1 Interactome in Hallucinations and Delusions

This research examines the genetic contribution of the DISC1 interactome to specific psychotic symptomatology, with a particular focus on hallucinations and delusions in schizophrenia and bipolar disorder. Psychotic disorders are characterized by severe manifestations, including hallucinations, delusions, and disorganized behavior. However, the molecular support of these specific symptoms remain poorly studied. The aim of this study was to investigate whether genetic variation within the DISC1 interactome is associated with distinct psychotic phenotypes. Phenotypic characterization revealed a high prevalence of auditory hallucinations and delusions of reference among the cases. Genotyping was conducted using the Illumina Infinium® PsychArray platform, focusing on 91 genes within the DISC1 interactome. Rigorous quality control metrics were applied to ensure data integrity. Single-nucleotide polymorphism (SNP) association analyses were performed using PLINK, incorporating relevant covariates such as age, sex, genetic ancestry components, and substance use. Gene-level and gene-set analyses were conducted in parallel using MAGMA, with functional annotation derived from Gene Ontology and KEGG pathways. Our findings enhance our understanding of the polygenic architecture underlying psychosis, suggesting that specific molecular mechanisms are implicated in the etiology of different hallucinatory and delusional phenotypes.

本研究探讨了精神分裂症断裂基因1（DISC1）相互作用组对特定精神病性症状的遗传贡献，重点聚焦于精神分裂症与双相情感障碍患者的幻听及妄想症状。精神病性障碍以幻觉、妄想及行为紊乱等严重临床表现为特征，但针对此类特异性症状的分子机制研究尚未得到充分开展。本研究旨在探究DISC1相互作用组内的遗传变异是否与不同精神病性表型存在关联。表型特征分析显示，本研究纳入的病例中，幻听与关系妄想的患病率较高。基因分型采用Illumina Infinium® 精神病基因分型平台，聚焦于DISC1相互作用组内的91个基因。本研究应用了严格的质量控制指标以保障数据完整性。单核苷酸多态性（SNP）关联分析采用PLINK软件进行，并纳入年龄、性别、遗传祖先成分及物质使用情况等相关协变量。本研究同时采用MAGMA开展基因水平与基因集分析，功能注释源自基因本体（GO）与京都基因与基因组百科全书（KEGG）通路数据库。本研究结果加深了我们对精神病背后多基因调控架构的认知，提示特定分子机制参与了不同幻听与妄想表型的病因发生过程。