Current literature suggests that people with psychiatric disorders have a higher risk of COVID-19 infection and a worse prognosis of the disease. We aimed to study the genetic contribution to these associations across seven psychiatric disorders as well as a general psychopathology factor (P-factor) and determine whether these are unique or shared across psychiatric disorders using statistical genetic techniques. Using the largest available genome-wide association studies (GWAS), we found a significant genetic overlap between depression, ADHD, PTSD, and the P-factor with both COVID-19 infection and hospitalization, and between anxiety and COVID-19 hospitalization. We used pairwise GWAS to examine this overlap on a fine-grained scale and identified specific regions of the genome shared between several psychiatric disorders, the P-factor, and COVID-19. Gene-based analysis in these genomic regions suggested possible links with immune-related pathways such as thyroid homeostasis, inflammation, and stress response. Finally, we show preliminary evidence for causal associations between depression, ADHD, PTSD, and the P-factor, and higher COVID-19 infection and hospitalization using Mendelian Randomization and Latent Causal Variable methods. Our results support the hypothesis that the relationship between psychiatric disorders and COVID-19 risk is likely due to shared alterations in immune-related pathways and is not a result of environmental factors alone, shedding light on potentially viable therapeutic targets.

目前的文献表明，患有精神疾病的人感染 COVID-19 的风险较高，且该疾病的预后较差。我们的目的是研究七种精神疾病以及一般精神病理学因素（P 因子）对这些关联的遗传贡献，并使用统计遗传技术确定这些因素在精神疾病之间是独特的还是共有的。利用最大的可用全基因组关联研究 (GWAS)，我们发现抑郁症、ADHD、PTSD 和 P 因子与 COVID-19 感染和住院治疗之间以及焦虑与 COVID-19 住院治疗之间存在显着的遗传重叠。我们使用成对 GWAS 在细粒度范围内检查这种重叠，并确定了几种精神疾病、P 因子和 COVID-19 之间共享的基因组特定区域。对这些基因组区域进行的基于基因的分析表明，它们可能与甲状腺稳态、炎症和应激反应等免疫相关途径存在联系。最后，我们使用孟德尔随机化和潜在因果变量方法，展示了抑郁症、ADHD、PTSD 和 P 因子与较高的 COVID-19 感染率和住院率之间存在因果关系的初步证据。我们的结果支持这样的假设，即精神疾病与 COVID-19 风险之间的关系可能是由于免疫相关途径的共同改变所致，而不仅仅是环境因素的结果，这揭示了潜在可行的治疗靶点。