Herpes simplex virus and Alzheimer's disease: a Mendelian randomization study

Neurobiol Aging. 2021 Mar;99:101.e11-101.e13. doi: 10.1016/j.neurobiolaging.2020.09.025. Epub 2020 Oct 9.


This study assessed if any herpes simplex virus (HSV) infection was a genetically valid target for late-onset Alzheimer's disease (AD) using 2-sample Mendelian randomization. We applied strong (p-value <5×10-6) and independent (r2 < 0.05) genetic variants for any HSV infection (n = 450,581) to genome wide association studies of cognitive function (n = 300,486), and late-onset AD (n = 455,258) to obtain estimates. Genetically predicted log odds of any HSV infection was not associated with cognitive function (mean difference 0.0004 per any HSV infection, 95% confidence interval (CI) -0.001 to 0.001), or late-onset AD (odds ratio (OR) 0.999, 95% CI 0.998-1.001). Different genetic variant selections produced similar results. Any HSV infection does not appear to be a genetically valid target of intervention in late-onset AD, suggesting a rethink of the relevance of any HSV infection to late-onset AD.

Keywords: Alzheimer's disease; Cognition; Herpes simplex virus; Mendelian randomization.

MeSH terms

  • Age of Onset
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics*
  • Female
  • Genetic Variation*
  • Genome-Wide Association Study*
  • Herpes Simplex / complications*
  • Herpes Simplex / genetics*
  • Humans
  • Male
  • Mendelian Randomization Analysis
  • Negative Results