研究免疫介导疾病集群与精神疾病之间的遗传联系。
Examining the genetic links between clusters of immune-mediated diseases and psychiatric disorders.
作者信息
Breunig Sophie, Lee Younga Heather, Karlson Elizabeth W, Krishnan Arjun, Lawrence Jeremy M, Schaffer Lukas S, Grotzinger Andrew D
机构信息
Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
出版信息
Transl Psychiatry. 2025 Jul 21;15(1):252. doi: 10.1038/s41398-025-03470-9.
Extant phenotypic and genetic literature has established consistent relationships between autoimmune, autoinflammatory, and psychiatric disorders. However, a comprehensive model investigating the association between a broad range of psychiatric disorders and immune-mediated disease in a multivariate framework is lacking. We utilized Genomic Structural Equation Modeling (Genomic SEM) to establish a factor structure across 11 immune-mediated diseases. Genetic correlations between these immune factors were examined with five established factors across 13 psychiatric disorders. We develop and validate a new heterogeneity metric, Q, that quantifies the degree to which factor correlations are driven by more specific pairwise associations, which were further investigated in the form of residual genetic correlations. A four-factor model of immune-mediated diseases fit the data well and described a continuum from autoimmune to autoinflammatory diseases, reflecting autoimmune, celiac, mixed pattern, and autoinflammatory diseases. Analyses revealed six significant factor correlations between the immune and psychiatric factors, including autoimmune and mixed pattern diseases with the substance use factors, autoinflammatory diseases and mixed pattern diseases with the internalizing factor, autoinflammatory diseases with the compulsive disorders factor, and autoinflammatory diseases with the schizophrenia/bipolar factor. Additionally, we find evidence of divergence in associations within factors as indicated by Q and 10 significant residual genetic correlations between individual psychiatric disorders and immune-mediated diseases. The results suggest 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.
现有的表型和基因文献已经确立了自身免疫性疾病、自身炎症性疾病和精神疾病之间的一致关系。然而,缺乏一个在多变量框架下研究广泛精神疾病与免疫介导疾病之间关联的综合模型。我们利用基因组结构方程模型(Genomic SEM)来建立11种免疫介导疾病的因子结构。研究了这些免疫因子之间的遗传相关性与13种精神疾病中已确立的5个因子之间的关系。我们开发并验证了一种新的异质性指标Q,该指标量化了因子相关性由更具体的成对关联驱动的程度,并以残差遗传相关性的形式对其进行了进一步研究。免疫介导疾病的四因子模型与数据拟合良好,描述了从自身免疫性疾病到自身炎症性疾病的连续谱,反映了自身免疫性疾病、乳糜泻、混合模式疾病和自身炎症性疾病。分析揭示了免疫因子和精神因子之间的六个显著因子相关性,包括自身免疫性疾病和混合模式疾病与物质使用因子、自身炎症性疾病和混合模式疾病与内化因子、自身炎症性疾病与强迫症因子以及自身炎症性疾病与精神分裂症/双相情感障碍因子。此外,正如Q所表明的,我们发现因子内关联存在差异的证据,以及个体精神疾病与免疫介导疾病之间的10个显著残差遗传相关性。结果表明,先前描述的特定精神疾病与免疫介导疾病之间的关系通常捕获了我们基因组因子所索引的更广泛的风险共享途径,但比所有精神疾病与免疫介导疾病之间的一般关联更具特异性。