Association study of the complement component C4 gene and suicide risk in schizophrenia.

IF 3 Q2 PSYCHIATRY Schizophrenia (Heidelberg, Germany) Pub Date : 2024-02-10 DOI:10.1038/s41537-024-00440-w
Mahbod Ebrahimi, Kowsar Teymouri, Cheng C Chen, Ayeshah G Mohiuddin, Jennie G Pouget, Vanessa F Goncalves, Arun K Tiwari, Clement C Zai, James L Kennedy
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Abstract

Schizophrenia is a severe mental illness and a major risk factor for suicide, with approximately 50% of schizophrenia patients attempting and 10% dying from suicide. Although genetic components play a significant role in schizophrenia risk, the underlying genetic risk factors for suicide are poorly understood. The complement component C4 gene, an immune gene involved in the innate immune system and located in the major histocompatibility complex (MHC) region, has been identified to be strongly associated with schizophrenia risk. In addition, recent findings have also suggested that the MHC region has been associated with suicide risk across disorders, making C4 a potential candidate of interest for studying suicidality in schizophrenia patients. Despite growing interest in investigating the association between the C4 gene and schizophrenia, to our knowledge, no work has been done to examine the potential of C4 variants as suicide risk factors in patients with schizophrenia. In this study, we investigated the association between different C4 copy number variants and predicted C4 brain expression with suicidal outcomes (suicide attempts/suicidal ideation). We directly genotyped 434 schizophrenia patients to determine their C4A and C4B copy number variants. We found the C4AS copy number to be marginally and negatively associated with suicide risk, potentially being protective against suicide attempts (OR = 0.49; p = 0.05) and suicidal ideation (OR = 0.65; p = 0.07). Furthermore, sex-stratified analyses revealed that there are no significant differences between males and females. Our preliminary findings encourage additional studies of C4 and potential immune dysregulation in suicide.

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补体成分 C4 基因与精神分裂症自杀风险的关联研究。
精神分裂症是一种严重的精神疾病,也是自杀的主要风险因素,约有 50%的精神分裂症患者试图自杀,10%的患者死于自杀。虽然遗传因素在精神分裂症风险中扮演着重要角色,但人们对自杀的潜在遗传风险因素却知之甚少。补体成分 C4 基因是一种参与先天性免疫系统的免疫基因,位于主要组织相容性复合体(MHC)区域,已被确认与精神分裂症风险密切相关。此外,最近的研究结果还表明,MHC 区域与各种疾病的自杀风险都有关联,这使得 C4 成为研究精神分裂症患者自杀倾向的潜在候选基因。尽管研究 C4 基因与精神分裂症之间关系的兴趣与日俱增,但据我们所知,还没有任何研究将 C4 基因变异作为精神分裂症患者自杀风险因素的可能性。在这项研究中,我们调查了不同的 C4 拷贝数变异和预测的 C4 大脑表达与自杀结果(自杀未遂/自杀意念)之间的关联。我们直接对 434 名精神分裂症患者进行了基因分型,以确定他们的 C4A 和 C4B 拷贝数变异。我们发现,C4AS拷贝数与自杀风险呈微弱负相关,对自杀未遂(OR = 0.49; p = 0.05)和自杀意念(OR = 0.65; p = 0.07)具有潜在保护作用。此外,性别分层分析表明,男性和女性之间没有显著差异。我们的初步研究结果鼓励对 C4 和自杀中潜在的免疫失调进行更多的研究。
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