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Cited by 17Alzheimer's disease research and treatmentsGenetic Associations and EpidemiologyDementia and Cognitive Impairment Research

Multigenomics Reveals the Causal Effect of Herpes Simplex Virus in Alzheimer’s Disease: A Two-Sample Mendelian Randomization Study

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Zhang, Yuwei, Qu, Jiaojiao, Luo, Li, Xu, Zhongshun, Zou, Xiao·2022·Frontiers in Genetics
DOI 10.3389/fgene.2021.773725PMC PMC8766664
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Abstract

In recent years, the herpes virus infectious hypothesis for Alzheimer’s disease (AD) has gained support from an increasing number of researchers. Herpes simplex virus (HSV) is a potential risk factor associated with AD. This study assessed whether HSV has a causal relationship with AD using a two-sample Mendelian randomization analysis model. Six single-nucleotide polymorphisms (SNPs) associated with HSV-1 and thirteen SNPs associated with HSV-2 were used as instrumental variables in the MR analysis. We estimated MR values of relevance between exposure and the risk of AD using inverse-variance weighted (IVW) method, MR-Egger regression (Egger), and weighted median estimator (WME). To make the conclusion more robust and reliable, sensitivity analyses and RadialMR were performed to evaluate the pleiotropy and heterogeneity. We found that anti-HSV-1 IgG measurements were not associated with risk of AD (OR, 0.96; 95% CI, 0.79–1.18; p = 0.736), and the same was true for HSV-2 (OR, 1.03; 95% CI, 0.94–1.12; p = 0.533). The findings indicated that any HSV infection does not appear to be a genetically valid target of intervention in 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 [35]

    The Results sections (3.1 and 3.2; page unavailable) report two-sample MR findings of no association between either HSV-1 or HSV-2 and AD, supporting one finding in the cited comparison. The Discussion (section 4; page unavailable) says the other MR studies it mentions reached the same result; this paper does not establish the claimed conflict between findings. (LLM, conf=0.83)

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Research works printed but not linked: 29

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Cited by

Sorted by citations

Authors
Zhang, Y., Qu, J., Luo, L., Xu, Z., & Zou, X.
Affiliations
Guizhou University (CN)
Corresponding author
Zou, Xiao
ORCID
Venue
Frontiers in Genetics
Publisher
Frontiers Media SA
Published
2022-01-05
Volume
12
Pages
773725-773725
ISSN
1664-8021 (ISSN-L)
DOI
10.3389/fgene.2021.773725
PMC
PMC8766664
OpenAlex
W4205909366
Cited by
17
References
1
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2023: 8 · 2022: 2
FWCI
2.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Genetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (31860037)
  • Science and Technology Program of Guizhou Province (qiankehe supported [2019]2405)
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, herpes simplex virus type 1, herpes simplex virus type 2, causal effects, single nucleotide polymorphisms, instrumental variables, pleiotropy

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