Importance Certain psychiatric and immune-related disorders are reciprocal risk factors. However, the nature of these associations is unclear. Objective To characterize the pleiotropy between psychiatric and immune-related traits, as well as risk factors of hypothesized relevance. Design, Setting, and Participants This genetic association study was conducted from July 10, 2020, to January 15, 2022. Analyses used genome-wide association (GWA) statistics related to 14 psychiatric traits; 13 immune-related phenotypes, ie, allergic, autoimmune, and inflammatory disorders; and 15 risk factors related to health-related behaviors, social determinants of health, and stress response. Genetically correlated psychiatric-immune pairs were assessed using 2-sample mendelian randomization (MR) with sensitivity analyses and multivariable adjustment for genetic associations of third variables. False discovery rate correction (Q value < .05) was applied for each analysis. Exposures Genetic associations. Main Outcomes and Measures Genetic correlations and MR association estimates with SEs and P values. A data-driven approach was used that did not test a priori planned hypotheses. Results A total of 44 genetically correlated psychiatric-immune pairs were identified, including 31 positive correlations (most consistently involving asthma, Crohn disease, hypothyroidism, and ulcerative colitis) and 13 negative correlations (most consistently involving allergic rhinitis and type 1 diabetes). Correlations with third variables were especially strong for psychiatric phenotypes. MR identified 7 associations of psychiatric phenotypes on immune-related phenotypes that were robust to multivariable adjustment, including the positive association of (1) the psychiatric cross-disorder phenotype with asthma (odds ratio [OR], 1.04; 95% CI, 1.02-1.06), Crohn disease (OR, 1.09; 95% CI, 1.05-1.14), and ulcerative colitis (OR, 1.09; 95% CI, 1.05-1.14); (2) major depression with asthma (OR, 1.25; 95% CI, 1.13-1.37); (3) schizophrenia with Crohn disease (OR, 1.12; 95% CI, 1.05-1.18) and ulcerative colitis (OR, 1.14; 95% CI, 1.07-1.21); and a negative association of risk tolerance with allergic rhinitis (OR, 0.77; 95% CI, 0.67-0.92). Conclusions and Relevance Results of this genetic association study suggest that genetic liability for psychiatric disorders was associated with liability for several immune disorders, suggesting that vertical pleiotropy related to behavioral traits (or correlated third variables) contributes to clinical associations observed in population-scale data.

中文翻译：

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连接精神病学和免疫相关表型的遗传相关性和遗传信息关联图谱。


重要性 某些精神疾病和免疫相关疾病是相互的危险因素。然而，这些协会的性质尚不清楚。目的 描述精神和免疫相关特征之间的多效性，以及假设相关的危险因素。设计、设置和参与者 这项遗传关联研究于 2020 年 7 月 10 日至 2022 年 1 月 15 日进行。分析使用与 14 种精神特征相关的全基因组关联 (GWA) 统计数据； 13种免疫相关表型，即过敏性、自身免疫性和炎症性疾病； 15 个与健康相关行为、健康社会决定因素和压力反应相关的风险因素。使用 2 样本孟德尔随机化 (MR) 以及敏感性分析和第三变量遗传关联的多变量调整来评估遗传相关的精神-免疫对。每次分析均应用错误发现率校正（Q 值 < .05）。暴露遗传关联。主要结果和措施 遗传相关性和 MR 关联估计与 SE 和 P 值。使用数据驱动的方法，没有测试先验计划的假设。结果共鉴定出 44 个遗传相关的精神免疫对，其中包括 31 个正相关（最一致涉及哮喘、克罗恩病、甲状腺功能减退症和溃疡性结肠炎）和 13 个负相关（最一致涉及过敏性鼻炎和 1 型糖尿病）。对于精神病表型来说，与第三个变量的相关性特别强。 MR 确定了精神科表型与免疫相关表型之间的 7 种关联，这些关联对多变量调整具有稳健性，包括 (1) 精神科跨疾病表型与哮喘的正相关性（比值比 [OR]，1.04；95% CI，1.02- 1.06）、克罗恩病（OR，1.09；95% CI，1.05-1.14）和溃疡性结肠炎（OR，1.09；95% CI，1.05-1.14）； (2) 重性抑郁伴哮喘（OR，1.25；95% CI，1.13-1.37）； （3）精神分裂症合并克罗恩病（OR，1.12；95% CI，1.05-1.18）和溃疡性结肠炎（OR，1.14；95% CI，1.07-1.21）；风险承受能力与过敏性鼻炎呈负相关（OR，0.77；95% CI，0.67-0.92）。这项遗传关联研究的结论和相关性结果表明，精神疾病的遗传倾向与多种免疫疾病的倾向相关，这表明与行为特征（或相关的第三变量）相关的垂直多效性有助于在人群规模数据中观察到的临床关联。