Lin Liu,1,2 Qiuli Zhang,1 Jianmin Chang,1,2 Kun Yang1 

1Department of Dermatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Peking Union Medical College, Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Beijing, People’s Republic of China

Correspondence: Kun Yang; Jianmin Chang, Email yangkun12.ky@icloud.com; changjianmin@medmail.com.cn

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.

Keywords: lichen sclerosus, diabetes mellitus, body mass index, Mendelian randomization