在表型和遗传文献中,自身免疫和自身炎性疾病与精神疾病有关。然而,目前还缺乏一个综合模型,在多变量框架中研究广泛的精神疾病和免疫介导的疾病之间的关联.
■本研究旨在建立基于免疫介导的疾病的遗传相关性的因子结构,并研究其与精神疾病簇的遗传关系。
■我们利用基因组结构方程模型(基因组SEM)建立了11种免疫介导疾病的因子结构。这些免疫因素之间的遗传相关性用13种精神疾病中的5种确定的因素进行了检查,代表强迫性,精神分裂症/躁郁症,神经发育,内化,和物质使用障碍。我们纳入了欧洲血统个体的GWAS汇总统计数据,样本量从1,223例Addison病病例到170,756例重度抑郁症病例。
■精神病和免疫介导的疾病因素与性状之间的遗传相关性,以确定遗传重叠。我们开发并验证了一种新的异质性指标,Q系数,量化了因子相关性由更具体的成对关联驱动的程度。我们还估计了一对精神疾病和免疫介导的疾病之间的残留遗传相关性。
■免疫介导的疾病的四因素模型很好地拟合了数据,并描述了从自身免疫疾病到自身炎性疾病的连续性。这四个因素反映了自身免疫,乳糜泻,混合模式,和自身炎症性疾病。分析揭示了免疫因素和精神因素之间的七个显着相关性,包括具有内在化和物质使用因素的自身免疫性和混合型疾病,和强迫性的自身炎症性疾病,精神分裂症/躁郁症,和内化因素。此外,我们发现了Q因子所表明的因子内关联存在差异的证据。这进一步得到了个体精神疾病和免疫介导疾病之间14个显著的残余遗传相关性的支持。
我们的研究结果揭示了免疫介导的疾病和精神疾病之间的遗传联系。当前的分析表明,先前描述的特定精神疾病和免疫介导的疾病之间的关系通常捕获了由我们的基因组因子索引的更广泛的风险共享途径。然而,在所有精神疾病和免疫介导的疾病中,比一般关联更具体。
■问题:免疫介导的疾病如何聚集在一起,以及它们如何与精神疾病集群相关?研究结果:免疫介导的疾病在自身免疫和自身炎症性疾病的重叠范围内聚集成四个因素。免疫介导的疾病因子和精神疾病因子之间存在七个显着的因子相关性,以及两个疾病性状之间更具体的成对关联。意义:免疫介导的疾病与精神疾病遗传相关。虽然一些关联似乎是由更一般的途径驱动的,我们还发现,一些共享信号对个体精神病-免疫性疾病对更具特异性。
UNASSIGNED: Autoimmune and autoinflammatory diseases have been linked to psychiatric disorders in the phenotypic and genetic literature. However, a comprehensive model that investigates the association between a broad range of psychiatric disorders and immune-mediated disease in a multivariate framework is lacking.
UNASSIGNED: This study aims to establish a factor structure based on the genetic correlations of immune-mediated diseases and investigate their genetic relationships with clusters of psychiatric disorders.
UNASSIGNED: We utilized Genomic Structural Equation Modeling (Genomic SEM) to establish a factor structure of 11 immune-mediated diseases. Genetic correlations between these immune factors were examined with five established factors across 13 psychiatric disorders representing compulsive, schizophrenia/bipolar, neurodevelopmental, internalizing, and substance use disorders. We included GWAS summary statistics of individuals of European ancestry with sample sizes from 1,223 cases for Addison\'s disease to 170,756 cases for major depressive disorder.
UNASSIGNED: Genetic correlations between psychiatric and immune-mediated disease factors and traits to determine genetic overlap. We develop and validate a new heterogeneity metric, Q Factor , that quantifies the degree to which factor correlations are driven by more specific pairwise associations. We also estimate residual genetic correlations between pairs of psychiatric disorders and immune-mediated diseases.
UNASSIGNED: A four-factor model of immune-mediated diseases fit the data well and described a continuum from autoimmune to autoinflammatory diseases. The four factors reflected autoimmune, celiac, mixed pattern, and autoinflammatory diseases. Analyses revealed seven significant factor correlations between the immune and psychiatric factors, including autoimmune and mixed pattern diseases with the internalizing and substance use factors, and autoinflammatory diseases with the compulsive, schizophrenia/bipolar, and internalizing factors. Additionally, we find evidence of divergence in associations within factors as indicated by Q Factor . This is further supported by 14 significant residual genetic correlations between individual psychiatric disorders and immune-mediated diseases.
UNASSIGNED: Our results revealed genetic links between clusters of immune-mediated diseases and psychiatric disorders. Current analyses indicate that previously described relationships between specific psychiatric disorders and immune-mediated diseases often capture broader pathways of risk sharing indexed by our genomic factors, yet are more specific than a general association across all psychiatric disorders and immune-mediated diseases.