Genetic Predisposition Between COVID-19 and Four Mental Illnesses: A Bidirectional, Two-Sample Mendelian Randomization Study

Ningning Liu; Jiang-Shan Tan; Lu Liu; Yufeng Wang; Lu Hua; Qiujin Qian

doi:10.3389/fpsyt.2021.746276

Genetic Predisposition Between COVID-19 and Four Mental Illnesses: A Bidirectional, Two-Sample Mendelian Randomization Study

Front Psychiatry. 2021 Oct 20:12:746276. doi: 10.3389/fpsyt.2021.746276. eCollection 2021.

Authors

Ningning Liu^{1

2}, Jiang-Shan Tan³, Lu Liu^{1

2}, Yufeng Wang^{1

2}, Lu Hua³, Qiujin Qian^{1

2}

Affiliations

¹ Peking University Sixth Hospital/Institute of Mental Health, Beijing, China.
² NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.
³ Thrombosis Center, Key Laboratory of Pulmonary Vascular Medicine, National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Background: The outbreak of 2019 coronavirus disease (COVID-19) has become a global pandemic. Although it has long been suspected that COVID-19 could contribute to the development of mental illness, and individuals with a pre-existing mental illness may have a higher risk of and poorer outcomes from COVID-19 infection, no evidence has established a causal association between them thus far. Methods: To investigate associations in support of a causal association between the severity of COVID-19 and mental illnesses, we leveraged large-scale genetic summary data from genome-wide association study (GWAS) summary datasets, including attention-deficit/hyperactivity disorder (ADHD) (n = 55,374), schizophrenia (n = 77,096), bipolar disorder (n = 51,710), and depression (n = 173,005), based on a previous observational study. The random-effects inverse-variance weighted method was conducted for the main analyses, with a complementary analysis of the weighted median and MR-Egger approaches and multiple sensitivity analyses assessing horizontal pleiotropy and removing outliers in two different COVID-19 databases. Results: The Mendelian randomization (MR) analysis indicated that ADHD [odds ratio (OR) = 1.297; 95% confidence interval (CI), 1.029-1.634; p = 0.028] increased the risk of hospitalization due to COVID-19. A similar association was obtained in MR sensitivity analyses of the weighted median. In addition, genetically predicted COVID-19 was significantly associated with schizophrenia (OR = 1.043; 95% CI, 1.005-1.082; p = 0.027). Conclusions: Although many studies have reported a causal relationship between COVID-19 and mental illness, our study shows that this increased risk is modest. However, considering the characteristics of ADHD that might further increase the individuals' vulnerability to being infected by COVID-19, the ongoing massive worldwide exposure to COVID-19, and the high burden of schizophrenia, we believe that it is necessary to offer preventative measures to these populations and to provide more evidence in understanding the neurological impact of COVID-19.

Keywords: COVID-19; GWAS; Mendelian randomization; mental illness; risk.