Externalizing traits: Shared causalities for COVID-19 and Alzheimer's dementia using Mendelian randomization analysis

Area of Science:

• Genetics and Epidemiology
• Neuroscience
• Infectious Diseases

Background:

• Externalizing traits are linked to coronavirus disease 2019 (COVID-19) and Alzheimer's dementia (AD).
• The causal nature of these associations remains unclear.
• Understanding these links is crucial for public health and disease management.

Purpose of the Study:

• To investigate the potential causal relationship between externalizing traits and the risk of COVID-19 and AD.
• To utilize a robust genetic approach to assess these associations.
• To identify shared underlying factors between externalizing behaviors, COVID-19, and AD.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) approach.
• Utilized over 200 single-nucleotide polymorphisms (SNPs) associated with externalizing traits.
• Applied inverse variance-weighted (IVW) method and sensitivity analyses (WM, PWM, MR-RAPS, leave-one-out).

Main Results:

• Significant causal associations were found between externalizing traits and increased risk of COVID-19 infection (OR=1.456) and hospitalization (OR=1.970).
• A causal link was also observed between externalizing traits and higher risk of AD (OR=1.077).
• Sensitivity analyses confirmed the robustness of these findings.

Conclusions:

• Externalizing traits appear to causally influence the risk and severity of COVID-19.
• Externalizing traits are also causally associated with an increased risk of Alzheimer's dementia.
• Shared genetic underpinnings may connect externalizing traits with both COVID-19 and AD pathophysiology.