Peer review process
Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, and public reviews.
Read more about eLife’s peer review process.Editors
- Reviewing EditorBian ZhuanWuhan University, Wuhan, China
- Senior EditorTadatsugu TaniguchiUniversity of Tokyo, Tokyo, Japan
Reviewer #1 (Public Review):
Ye et al. used Mendelian randomization method to evaluate the causative association between circulating immune cells and periodontitis and finally screened out three risk immune cells related to periodontitis. Overall, this is an important and novel piece of work that has the potential to contribute to our understanding of the causal relationship between circulating immune cells related to periodontitis. However, there are still some concerns that need to be addressed.
1. The authors used 1e-9 as the threshold to select effective instrumental variables (IVs), which should give the corresponding references. Meanwhile, the authors should test and discuss the potential impact of inconsistent thresholds for exposure (1e-9, 5e-6 were selected by the author respectively) and outcome IVs (5e-8) on the robustness of the results.
2. What is the reference for selecting Smoking, Fasting plasma glucose, and BMI as covariates? They do not seem to be directly related to immune cells as confounding factors.
3. It is not entirely clear about the correction of P-value for the total number of independent statistical tests.
4. The author used whole blood data to apply FUSION algorithm. Although whole blood is a representative site, the authors should add FUSION testing of periodontally relevant tissues, such as oral mucosa.
5. The authors chose gingival hyperplasia as a secondary validation phenotype of periodontitis in this study. However, gingival recession, as another important phenotype associated with periodontitis, should also be tested and discussed.
6. This study used GLIDE data as a replicated validation, but the results were inconsistent with FinnGen's dataset.
Reviewer #2 (Public Review):
This manuscript presents a well-designed study that combines multiple Mendelian randomization analyses to investigate the causal relationship between circulating immune cells and periodontitis. The main conclusions of the manuscript are appropriately supported by the statistics, and the methodologies used are comprehensive and rigorous.
These findings have significant implications for periodontal care and highlight the potential for systemic immunomodulation management on periodontitis, which is of interest to readers in the fields of periodontology, immunology, and epidemiology.
