Mendelian randomization study on the causal effect of herpes simplex virus infection on idiopathic pulmonary fibrosis

ABSTRACT

Background

Previous observational studies have shown that past infection of herpes simplex virus (HSV) is associated with idiopathic pulmonary fibrosis (IPF). The present study aims to identify the causal link between HSV infection (exposure factor) and IPF (outcome factor).

Research design and methods

To date, the largest publicly available genome-wide association study (GWAS) for HSV infection (1,595 cases and 211,856 controls from Finnish ancestry) and for IPF (1,028 cases and 196,986 controls from Finnish ancestry) were used to perform this two-sample Mendelian randomization (MR) study.

Results

We found no significant pleiotropy or heterogeneity of all selected nine HSV infection-associated genetic instrumental variants (IVs) in IPF GWAS dataset. Interestingly, we found that as HSV infection genetically increased, IPF risk increased based on an inverse-variance weighted (IVW) analysis (odds ratio [OR] = 1.280, 95% confidence interval [CI]: 1.048–1.563; p = 0.015) and weighted median (OR = 1.321, 95% CI: 1.032–1.692; p = 0.027).

Conclusions

Our analysis suggests a causal effect of genetically increased HSV infection on IPF risk. Thus, HSV infection may be a potential risk factor for IPF.

KEYWORDS:

• Herpes simplex virus
• idiopathic pulmonary fibrosis
• genome-wide association study
• Mendelian randomization
• genetic variants

Declarations of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

M Zhang and J Qiu worked on acquisition of data, analysis and interpretation, substantially revised and critically reviewed the article, taken responsibility to resolve any questions raised about the accuracy and integrity of the published work.

The two authors contributed equally to this work as first authors.

R Wang worked on the conception, study design, acquisition of data, analysis and interpretation, drafted and wrote, substantially revised, and critically reviewed the article.

Data availability statement

The summary statistics of the IPF-associated GWAS provided by ieu open gwas project and is available at https://gwas.mrcieu.ac.uk/datasets/finn-b-IPF. The summary statistics of HSV infection-associated GWAS provided by the FinnGen study and is available at https://www.finngen.fi/en/access_results. The MR analysis code can be found at https://mrcieu.github.io/TwoSampleMR/articles/index.html.

Additional information

Funding

This study was funded by grants from National Natural Science Foundation of China [32270933] and [82071758] and R&D Program of Beijing Municipal Education Commission [KZ202210025035].