■以前的观察性研究发现硬化苔藓(LS)与代谢状态有关,如糖尿病(DM)和体重指数(BMI)。然而,也有一些研究表明LS与DM和BMI无关.观察结果背后的机制尚不清楚。因此,这种关系的因果关系仍然未知。在这项研究中,进行了双向双样本孟德尔随机化(MR)来研究DM,BMI,和LS。
■与DM(包括1型和2型糖尿病)相关的工具变量,和BMI从全基因组关联研究(GWAS)和GWAS荟萃分析中确定。LS的GWAS数据来自2022年发布的第八版FinnGen生物数据库。反向方差加权(IVW),加权中位数,和MR-Egger方法用于进行双向双样本MR分析。此后,研究了异质性和水平多效性,以确定结果是否受单核苷酸多态性(SNP)的影响.
■我们发现缺乏证据证明DM的因果关系,和BMI在LS上的逆方差加权(1型糖尿病,OR=0.97,95%CI=0.91-1.04,p=0.429;2型糖尿病,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)。在另一个方向,结果还显示,LS对DM和BMI无显著因果效应.
■这项MR分析表明,DM和BMI与LS在两个方向上都没有显着的因果关系,这与之前报告的正相关的观察性研究相矛盾。潜在的混杂因素可能有助于先前观察到的关联,需要进一步的研究。
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.