Zhao Baokang, Zhong Qiangqiang, Liu Xiangjie
Laboratory of Metabolic Abnormalities and Vascular Aging, Liyuan Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Geriatrics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Medicine (Baltimore). 2025 Jun 13;104(24):e42856. doi: 10.1097/MD.0000000000042856.
This study explores the causal link between celiac disease (CeD) and osteoporosis and measures the intermediary role of thyroid dysfunction in this relationship. Using genome-wide association studies summary data, we performed two-sample Mendelian randomization (MR) studies on genetically predicted CeD (11,812 cases, 23,649 individuals) and osteoporosis (462,933 samples, 7547 cases). We applied two-step MR to quantify the influence of CeD on osteoporosis, two-sample MR to validate the effects of potential mediators (type 1 and 2 diabetes, hyperthyroidism, hypothyroidism), and multivariate MR to estimate the effects of hyperthyroidism and hypothyroidism, and their joint influence. CeD contributes to the risk of osteoporosis (OR: 1.001, 95% CI: 1.000-1.001, P = 4.36E-07) and promotes both hyperthyroidism (OR: 1.001, 95% CI: 1.000-1.002, P = .0003) and hypothyroidism (OR: 1.004, 95% CI: 1.002-1.005, P = 2.24E-06). Hyperthyroidism and hypothyroidism account for 3.17% (95% CI: 2.29%, 5.19%) and 2.24% (95% CI: 1.61%, 3.65%) of the total effect of CeD on osteoporosis, respectively. Together, they explain 34.31% (95% CI: 24.72%, 56.05%) of the total effect. Our study confirms the causal effect between CeD and osteoporosis risk, in which thyroid dysfunction plays a mediating role. Increasing population-level thyroid function screening may lower this risk.
本研究探讨乳糜泻（CeD）与骨质疏松症之间的因果联系，并衡量甲状腺功能障碍在这种关系中的中介作用。利用全基因组关联研究汇总数据，我们对基因预测的CeD（11812例，23649人）和骨质疏松症（462933个样本，7547例）进行了两样本孟德尔随机化（MR）研究。我们应用两步MR来量化CeD对骨质疏松症的影响，两样本MR来验证潜在中介因素（1型和2型糖尿病、甲状腺功能亢进、甲状腺功能减退）的作用，以及多变量MR来估计甲状腺功能亢进和甲状腺功能减退的作用及其联合影响。CeD会增加骨质疏松症风险（比值比：1.001，95%置信区间：1.000 - 1.001，P = 4.36E - 07），并促进甲状腺功能亢进（比值比：1.001，95%置信区间：1.000 - 1.002，P = 0.0003）和甲状腺功能减退（比值比：1.004，95%置信区间：1.002 - 1.005，P = 2.24E - 06）。甲状腺功能亢进和甲状腺功能减退分别占CeD对骨质疏松症总影响的3.17%（95%置信区间：2.29%，5.19%）和2.24%（95%置信区间：1.61%，3.65%）。它们共同解释了总影响的34.31%（95%置信区间：24.72%，56.05%）。我们的研究证实了CeD与骨质疏松症风险之间的因果关系，其中甲状腺功能障碍起中介作用。提高人群水平的甲状腺功能筛查可能会降低这种风险。
