Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis

Qingcong Zheng; Du Wang; Rongjie Lin; Yuchao Chen; Haoen Huang; Zixing Xu; Chunfu Zheng; Weihong Xu

doi:10.3389/fnins.2023.1299122

Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis

Front Neurosci. 2023 Dec 12:17:1299122. doi: 10.3389/fnins.2023.1299122. eCollection 2023.

Authors

Qingcong Zheng^#^{1

2}, Du Wang^#³, Rongjie Lin^#⁴, Yuchao Chen⁵, Haoen Huang¹, Zixing Xu^{1

2}, Chunfu Zheng⁶, Weihong Xu^{1

2}

Affiliations

¹ Department of Spinal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
² Department of Orthopedics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
³ Arthritis Clinical and Research Center, Peking University People's Hospital, Beijing, China.
⁴ Department of Orthopedic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
⁵ Department of Paediatrics, Fujian Provincial Hospital South Branch, Fuzhou, China.
⁶ Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada.

^# Contributed equally.

Abstract

Background: The causal associations between infections with human herpes viruses (HHVs) and amyotrophic lateral sclerosis (ALS) has been disputed. This study investigated the causal associations between herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, and HHV-7 infections and ALS through a bidirectional Mendelian randomization (MR) method.

Methods: The genome-wide association studies (GWAS) database were analyzed by inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. MR-Egger intercept test, MR-PRESSO test, Cochran's Q test, funnel plots, and leaveone-out analysis were used to verify the validity and robustness of the MR results.

Results: In the forward MR analysis of the IVW, genetically predicted HSV infections [odds ratio (OR) = 0.9917; 95% confidence interval (CI): 0.9685-1.0154; p = 0.4886], HSV keratitis and keratoconjunctivitis (OR = 0.9897; 95% CI: 0.9739-1.0059; p = 0.2107), anogenital HSV infection (OR = 1.0062; 95% CI: 0.9826-1.0304; p = 0.6081), VZV IgG (OR = 1.0003; 95% CI: 0.9849-1.0160; p = 0.9659), EBV IgG (OR = 0.9509; 95% CI: 0.8879-1.0183; p = 0.1497), CMV (OR = 0.9481; 95% CI: 0.8680-1.0357; p = 0.2374), HHV-6 IgG (OR = 0.9884; 95% CI: 0.9486-1.0298; p = 0.5765) and HHV-7 IgG (OR = 0.9991; 95% CI: 0.9693-1.0299; p = 0.9557) were not causally associated with ALS. The reverse MR analysis of the IVW revealed comparable findings, indicating no link between HHVs infections and ALS. The reliability and validity of the findings were verified by the sensitivity analysis.

Conclusion: According to the MR study, there is no evidence of causal associations between genetically predicted HHVs (HSV, VZV, EBV, CMV, HHV-6, and HHV-7) and ALS.

Keywords: Mendelian randomization; amyotrophic lateral sclerosis; causal association; human herpes virus; neurodegenerative diseases.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The Natural Science Foundation of Fujian Province (No. 2020 J01947, No. 2021 J02035) and Fujian Provincial Health Technology Project (No. 2020CXA039, No. 2021CXA019) supported the study.