Externalizing traits: shared causalities for COVID-19 and alzheimer’s dementia using mendelian randomization analysis

Abstract Background Externalizing traits have been related with the outcomes of coronavirus disease 2019 (COVID-19) and Alzheimer’s dementia (AD), however, whether these associations are causal remains unknown. Methods We used two-sample Mendelian randomization (MR) approach with more than 200 single-nucleotide polymorphisms (SNPs) for externalizing traits to explore the causal associations of externalizing traits with the risk of COVID-19 (infected COVID-19, hospitalized COVID-19, and severe COVID-19) or AD based on the summary data. The inverse-variance weighted method (IVW) was used to estimate the main effect, followed by several sensitivity analyses. Results IVW analysis showed significant associations of externalizing traits with COVID-19 infection (odds ratio [OR] = 1.456, 95% confidence interval [95% CI] = 1.224–1.731), hospitalized COVID-19 (OR = 1.970, 95% CI = 1.374–2.826), and AD (OR = 1.077, 95% CI = 1.037–1.119). The results were consistent using WM, PWM, MR-RAPS, and leave-one-out sensitivity analyses. Conclusion Our findings assist in exploring the causal effect of externalizing traits on the pathophysiology of infection and severe infection of COVID-19 and AD. Furthermore, our study provides evidence that shared externalizing traits underpin the two diseases.