An important contributor to the decreased life expectancy of individuals with schizophrenia is sudden cardiac death. Arrhythmic disorders may play an important role herein, but the nature of the relationship between schizophrenia and arrhythmia is unclear.

To assess shared genetic liability and potential causal effects between schizophrenia and arrhythmic disorders and electrocardiogram (ECG) traits.

We leveraged summary-level data of large-scale genome-wide association studies of schizophrenia (53 386 cases, 77 258 controls), arrhythmic disorders (atrial fibrillation, 55 114 cases, 482 295 controls; Brugada syndrome, 2820 cases, 10 001 controls) and ECG traits (heart rate (variability), PR interval, QT interval, JT interval and QRS duration, n = 46 952–293 051). We examined shared genetic liability by assessing global and local genetic correlations and conducting functional annotation. Bidirectional causal relations between schizophrenia and arrhythmic disorders and ECG traits were explored using Mendelian randomisation.

There was no evidence for global genetic correlation, except between schizophrenia and Brugada syndrome (rg = 0.14, 95% CIs = 0.06–0.22, P = 4.0E−04). In contrast, strong positive and negative local correlations between schizophrenia and all cardiac traits were found across the genome. In the most strongly associated regions, genes related to immune and viral response mechanisms were overrepresented. Mendelian randomisation indicated that liability to schizophrenia causally increases Brugada syndrome risk (beta = 0.14, CIs = 0.03–0.25, P = 0.009) and heart rate during activity (beta = 0.25, CIs = 0.05–0.45, P = 0.015).

Despite little evidence for global genetic correlation, specific genomic regions and biological pathways emerged that are important for both schizophrenia and arrhythmia. The putative causal effect of liability to schizophrenia on Brugada syndrome warrants increased cardiac monitoring and early medical intervention in people with schizophrenia.

精神分裂症患者预期寿命缩短的一个重要原因是心源性猝死。心律失常障碍可能在此处起重要作用，但精神分裂症和心律失常之间关系的性质尚不清楚。

评估精神分裂症与心律失常障碍和心电图 （ECG） 特征之间的共同遗传倾向和潜在因果关系。

我们利用了精神分裂症（53 386 例，77 258 例对照）、心律失常疾病（心房颤动，55 114 例，482 295 例对照;Brugada 综合征，2820 例，10 001 例对照）和 ECG 特征（心率（变异性）、PR 间期、QT 间期、JT 间期和 QRS 时限，n = 46 952–293 051）。我们通过评估全球和局部遗传相关性并进行功能注释来检查共同的遗传责任。使用孟德尔随机化探讨了精神分裂症和心律失常障碍与 ECG 特征之间的双向因果关系。

除了精神分裂症和 Brugada 综合征之间 （rg = 0.14,95% CI = 0.06–0.22，P = 4.0E-04） 外，没有证据表明 全球遗传相关性。相比之下，在整个基因组中发现精神分裂症与所有心脏特征之间存在很强的正负局部相关性。在相关性最强的区域，与免疫和病毒反应机制相关的基因被过度代表。孟德尔随机化表明，精神分裂症易感性因果关系增加 Brugada 综合征风险 （beta = 0.14，CI = 0.03-0.25，P = 0.009） 和活动期间的心率 （beta = 0.25，CI = 0.05-0.45，P = 0.015）。

尽管几乎没有证据表明全球遗传相关性，但出现了对精神分裂症和心律失常都很重要的特定基因组区域和生物途径。精神分裂症易感性对 Brugada 综合征的推定因果效应需要加强对精神分裂症患者的心脏监测和早期医疗干预。