Herpes simplex virus and Alzheimer’s disease: a Mendelian randomization study
Abstract
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 -6 ) and independent (r 2 < 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.
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There are conflicting findings when examining the causal relationship between HSV-1 and HSV-2 with AD using two-sample Mendelian randomization.
“There are conflicting findings when examining the causal relationship between HSV-1 and HSV-2 with AD using two-sample Mendelian randomization [34,35].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [34]
Cites
Evaluating the potential role of pleiotropy in Mendelian randomization studies
Hemani, G., Bowden, J., & Davey Smith, G. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy163 · Cited by 1,496 · see citing works
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HSV-1 and Alzheimer’s disease: more than a hypothesis
Piacentini, R., De Chiara, G., Li Puma, D. D., Ripoli, C., Marcocci, M. E., Garaci, E., Palamara, A. T., & Grassi, C. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00097 · Cited by 130 · see citing works
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Herpesvirus infections and Alzheimer's disease: a mendelian randomization study
Huang, S.-Y., Yang, Y.-X., Kuo, K., Li, H.-Q., Shen, X.-N., Chen, S.-D., Cui, M., Tan, L., Dong, Q., & Yu, J.-T. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00905-5 · Cited by 82 · see citing works
Duggan, M. R., Peng, Z., An, Y., Kitner Triolo, M. H., Shafer, A. T., Davatzikos, C., Erus, G., Karikkineth, A., Lewis, A., Moghekar, A., et al. (2022) · Neurology · doi:10.1212/wnl.0000000000201036 · Cited by 24 · see citing works
Warren‐Gash, C., Cadogan, S. L., Nicholas, J. M., Breuer, J. M., Shah, D., Pearce, N., Shiekh, S., Smeeth, L., Farlow, M. R., Mori, H., et al. (2022) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51669 · Cited by 11 · see citing works
What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease?
Brutkiewicz, R. R., Cao, W., Morgan, D., Reis, R. S. D., Suryadevara, V., Willette, A. A., Willette, S. A., Wyatt-Johnson, S. K., & Duggan, M. R. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.05.009 · Cited by 3 · see citing works
- Authors
- Kwok, M. K., & Schooling, C. M.
- Affiliations
- University of Hong Kong (HK)
- City University of New York (US)
- Corresponding author
- Schooling, Catherine Mary
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 99
- Pages
- 101.e11-101.e13
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W3091930142
- Cited by
- 55
- References
- 3
- Citations by year
- 2025: 8 · 2024: 17 · 2023: 9 · 2022: 12 · 2021: 9
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- herpes simplex virus, Alzheimer's disease, late-onset Alzheimer's disease, herpes simplex, cognitive function, genetic variants, causal inference, therapeutic target
- MeSH terms
- Negative Results, Alzheimer Disease, Female, Herpes Simplex, Humans, Male, Genetic Variation, Age of Onset, Genome-Wide Association Study, Mendelian Randomization Analysis
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