THE CONTRIBUTION OF COPY NUMBER VARIANTS TO SCHIZOPHRENIA: FROM A GENOME-WIDE STUDY IN EAST ASIAN POPULATIONS

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology Pub Date : 2024-10-01 DOI:10.1016/j.euroneuro.2024.08.069

Yu Chen , Qidi Feng , Mingrui Yu , Stanley Center Asia , Max Lam , Akira Sawa , Jingsong Tang , Xiancang Ma , Wei J Chen , Shengying Qin , Weihua Yue , Tian Ge , Hailiang Huang

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引用次数: 0

Abstract

Here, we present a study on rare copy number variants (rCNVs) in schizophrenia, emphasizing the shift from traditional European (EUR) populations to a large East Asian (EAS) cohort, the largest to date, with 20,903 cases and 23,258 controls. The study confirms previous findings about the heightened genome-wide rCNV burden in schizophrenia patients within this EAS cohort. A combined meta-analysis of EAS and EUR cohorts, totaling 38,409 cases and 40,009 controls, identified 15 significant rCNV loci. Of these, five were novel, found at locations 1q21.2, 8p21.3, 11q13.1, 19p13.3, and 19q13.42. The comparison between EAS and EUR data suggested that differences in rCNV frequencies contribute to variability in discovery power across these populations rather than differences in genetic effect sizes.

Among the eight rCNV loci implicated in the PGC EUR study with genome-wide significance, seven had rCNVs captured in the EAS dataset, among which three achieved genome-wide significance (P<6.88e-5, 22q11.21 deletion, 3q29 deletion, and 16p11.2 duplication) and an additional three reached nominal significance (P < 0.05, 1q21.1 deletion, 16p11.2 deletion, and 7q11.23 duplication). None of these loci showed a significant difference in effect size between the two populations.

rCNVs, particularly, are significant as they have a pronounced potential to disrupt neuronal development and synaptic connectivity. The discovery of novel rCNV loci in the EAS population enriches our understanding of the genetic architecture of schizophrenia and underscores the potential influence of rCNVs on neurodevelopmental processes. Comparing rCNV profiles between EAS and EUR cohorts illuminates how population-specific genomic structures can influence the prevalence and impact of these genetic variations.

The current findings underscore the variability in genetic factors influencing schizophrenia across different populations and highlight the necessity of expanding genetic studies to include diverse populations beyond those of European descent. Identifying novel loci in the EAS population not only enriches our understanding of the genetic architecture of schizophrenia but also suggests that population-specific genetic variations could be crucial for tailoring more effective diagnostics and treatments.

Furthermore, this study enhances our understanding of the genetic diversity and complexity of schizophrenia, contributing valuable insights into how different populations may exhibit unique genetic profiles that influence the disease. By exploring these distinctions, the research advocates for a more inclusive approach to genetic research, which is essential for developing global health strategies and interventions sensitive to genetic diversity. This aligns with the conference theme by emphasizing the importance of including diverse genetic backgrounds to achieve a more comprehensive understanding of psychiatric disorders.

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拷贝数变异对精神分裂症的影响：来自东亚人群的全基因组研究

在这里，我们介绍了一项关于精神分裂症罕见拷贝数变异（rCNVs）的研究，强调了从传统欧洲（EUR）人群到大型东亚（EAS）队列的转变，这是迄今为止最大的队列，其中有 20903 例病例和 23258 例对照。这项研究证实了之前的发现，即在东亚队列中，精神分裂症患者的全基因组 rCNV 负担加重。对EAS队列和EUR队列（共38,409例病例和40,009例对照）的合并荟萃分析确定了15个重要的rCNV位点。其中有五个是新发现的，分别位于 1q21.2、8p21.3、11q13.1、19p13.3 和 19q13.42。EAS 和 EUR 数据的比较表明，rCNV 频率的差异导致了这些人群发现能力的差异，而不是遗传效应大小的差异。在 PGC EUR 研究中具有全基因组意义的 8 个 rCNV 位点中，有 7 个在 EAS 数据集中捕获到了 rCNV，其中 3 个达到了全基因组意义（P<6.88e-5，22q11.21 缺失、3q29 缺失和 16p11.2 重复），另外 3 个达到了名义意义（P <0.05，1q21.1 缺失、16p11.2 缺失和 7q11.23 重复）。这些基因位点在两个人群中的效应大小均无显著差异。rCNVs 尤为重要，因为它们具有明显的破坏神经元发育和突触连接的潜力。在 EAS 群体中发现新的 rCNV 基因座丰富了我们对精神分裂症遗传结构的了解，并强调了 rCNV 对神经发育过程的潜在影响。目前的研究结果凸显了不同人群中影响精神分裂症的遗传因素的差异性，并强调了将遗传研究扩展到欧洲后裔以外的不同人群的必要性。在EAS人群中发现新的基因位点不仅丰富了我们对精神分裂症遗传结构的了解，而且还表明特定人群的遗传变异可能对定制更有效的诊断和治疗方法至关重要。此外，这项研究还增强了我们对精神分裂症遗传多样性和复杂性的了解，对不同人群如何表现出影响该疾病的独特遗传特征提供了宝贵的见解。通过探索这些区别，这项研究倡导以更具包容性的方法开展基因研究，这对于制定对基因多样性敏感的全球健康战略和干预措施至关重要。这与会议主题不谋而合，强调了纳入不同遗传背景对更全面地了解精神疾病的重要性。

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来源期刊

European Neuropsychopharmacology 医学-精神病学

CiteScore

10.30

自引率

5.40%

发文量

730

审稿时长

41 days

期刊介绍： European Neuropsychopharmacology is the official publication of the European College of Neuropsychopharmacology (ECNP). In accordance with the mission of the College, the journal focuses on clinical and basic science contributions that advance our understanding of brain function and human behaviour and enable translation into improved treatments and enhanced public health impact in psychiatry. Recent years have been characterized by exciting advances in basic knowledge and available experimental techniques in neuroscience and genomics. However, clinical translation of these findings has not been as rapid. The journal aims to narrow this gap by promoting findings that are expected to have a major impact on both our understanding of the biological bases of mental disorders and the development and improvement of treatments, ideally paving the way for prevention and recovery.