https://orcid.org/0000-0002-3371-9375
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Abstract
Background
Previous observational studies have found that lichen sclerosus (LS) is associated with metabolic statuses, such as diabetes mellitus (DM) and body mass index (BMI). However, there are also some studies showing that LS is not related to DM and BMI. The mechanism behind observational results is still unclear. Therefore, the causality of this relationship remains unknown. In this study, a bidirectional two-sample Mendelian randomization (MR) was conducted to investigate the correlation between DM, BMI, and LS.
Methods
The instrumental variables related to DM (including type 1 and type 2 diabetes), and BMI were identified from genome-wide association studies (GWAS) and a GWAS meta-analysis. The GWAS data for LS was from obtained the eighth edition of the FinnGen biological database released in 2022. Inverse variance weighted (IVW), weighted median, and MR-Egger methods were used to conduct a bidirectional two-sample MR analysis. Thereafter, the heterogeneity and horizontal pleiotropy were examined to determine whether the results were affected by a single-nucleotide polymorphism (SNP).
Results
We found a lack of evidence for the causal association of DM, and BMI on LS in inverse variance weighted (type 1 diabetes, OR=0.97, 95% CI=0.91–1.04, p=0.429; type 2 diabetes, OR=0.91, 95% CI=0.82–1.00, p=0.0511; BMI, OR=0.92, 95% CI=0.73–1.15, p=0.4554). In the other direction, the results also showed that LS had no significant causal effect on DM and BMI.
Conclusion
This MR analysis demonstrated no significant causal relationship between DM and BMI with LS in both directions, which contradicts previous observational studies reporting a positive association. Potential confounding factors may contribute to previously observed associations, and further research is necessary.
Abbreviations
LS, Lichen sclerosus; GLS, Genitalia lichen sclerosus; DM, Diabetes mellitus; T1D, Type 1 diabetes; T2D, Type 2 diabetes; BMI, Body mass index; MR, Mendelian randomization; GWAS, Genome-wide association studies; IVW, Inverse variance weighted; IV, Instrumental variable; SNP, Single-nucleotide polymorphism.
Data Sharing Statement
All analyses were conducted using publicly available data. The GWAS summary data for type 1 diabetes and BMI are available in GWAS catalog, at https://gwas.mrcieu.ac.uk/. The summary-level data of type 2 diabetes were acquired from a GWAS meta-analysis. The GWAS summary data for lichen sclerosus are available in FinnGen, at https://www.finngen.fi/en.
Ethics Approval and Consent to Participate
According to Article 32 of the Measures for Ethical Review of Life Science and Medical Research Involving Human Beings adopted by the National Science and Technology Ethics Committee of the People’s Republic of China, ethical review can be exempted because the data used in this study do not cause any harm to human beings, do not involve any sensitive personal information or commercial interests, and the databases selected are open and legal. Therefore, approval from a new ethics review committee is not required.
Acknowledgments
We want to acknowledge the participants and investigators of the FinnGen study. We thank all the participants and investigators who provided valuable genetic summary statistics for this study.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare they have no conflicts of interest.