Virus exposure and neurodegenerative disease risk across national biobanks

Abstract

With recent findings connecting the Epstein-Barr virus to an increased risk of multiple sclerosis and growing concerns regarding the neurological impact of the coronavirus pandemic, we examined potential links between viral exposures and neurodegenerative disease risk. Using time series data from FinnGen for discovery and cross-sectional data from the UK Biobank for replication, we identified 45 viral exposures significantly associated with increased risk of neurodegenerative disease and replicated 22 of these associations. The largest effect association was between viral encephalitis exposure and Alzheimer's disease. Influenza with pneumonia was significantly associated with five of the six neurodegenerative diseases studied. We also replicated the Epstein-Barr/multiple sclerosis association. Some of these exposures were associated with an increased risk of neurodegeneration up to 15 years after infection. As vaccines are currently available for some of the associated viruses, vaccination may be a way to reduce some risk of neurodegenerative disease.

Keywords: Alzheimer’s disease; Parkinson’s disease; amyotrophic lateral sclerosis; encephalitis; generalized dementia; influenza; multiple sclerosis; varicella-zoster; vascular dementia; viral exposure.

Figure 1:. Graphical Summary of Hazard Ratio Lag for Replicated Viral/NDD Pairs

Graphical summary of hazard ratio lag for replicated associations between viral exposures and neurodegenerative diseases shows increased risk of neurodegeneration even 15 years prior to disease onset. The size of the circle on each line represents relative sample size overlap for the viral exposure and the associated NDD at that time point. The position of the circle on each line denotes the HRs with whiskers showing the 95% CIs, represented on a log scaled x axis. The association between Epstein-Barr virus and multiple sclerosis was included at the top as a reference for scale.