A Two-Sample Mendelian Randomization Study of Ulcerative Colitis and Osteoporosis

目的：本研究采用两样本孟德尔随机化方法来探讨溃疡性结肠炎与骨质疏松症之间的因果关系。方法：获取和分析来自欧洲人群的全基因关联研究(GWAS)的汇总数据，并筛选出与溃疡性结肠炎密切相关的工具变量，其中涵盖了27,432例溃疡性结肠炎患者和212,778例骨质疏松症患者的样本，运用逆方差加权法(IVW)、MR-Egger回归和加权中位数法等方法进行两样本孟德尔随机化分析，评估溃疡性结肠炎与骨质疏松症之间的关联，以P值分析溃疡性结肠炎对骨质疏松风险的因果关系，使用OR值作为效应量。结果：共纳入了85个SNPs作为工具变量，MR-Egger回归的结果显示没有发现基因水平的多效性(P = 0.1949)。逆方差加权法的结果表明，溃疡性结肠炎与骨质疏松症存在因果关系(P = 0.0439 Objective: This study utilized a two-sample Mendelian randomization method to investigate the causal link between ulcerative colitis and osteoporosis. Methods: We sourced and analyzed pooled data from genome-wide association studies (GWAS) among individuals of European descent, pinpointing instrumental variables closely related to ulcerative colitis. The study included samples from 27,432 ulcerative colitis patients and 212,778 osteoporosis patients. We performed two-sample Mendelian randomization analyses employing the inverse variance weighting (IVW) method, MR-Egger regression, and the weighted median approach. The connection between ulcerative colitis and osteoporosis was evaluated, and the causal effect of ulcerative colitis on osteoporosis risk was scrutinized through P-value analysis, with the odds ratio (OR) serving as the effect measure. Results: A sum of 85 SNPs was incorporated as instrumental variables. The MR-Egger regression demonstrated an absence of genetic pleiotropy (P = 0.1949). Findings from the inverse variance weighting method pointed to a causal relationship between ulcerative colitis and osteoporosis (P = 0.0439 < 0.05), indicating a 5% heightened risk of osteoporosis for individuals with ulcerative colitis following logarithmic transformation (OR = 1.0589, 95%CI: 1.0015~1.1195). Upon synthesizing the analytical outcomes, we reached a conclusion that there exists a causal connection between ulcerative colitis and osteoporosis.