Abstract：
Osteoporosis is a major clinical problem in many autoimmune diseases, including primary biliary cholangitis (PBC), the most common autoimmune liver disease. Osteoporosis is a major cause of fracture and related mortality. However, it remains unclear whether PBC confers a causally risk-increasing effect on osteoporosis. Herein, we aimed to investigate the causal relationship between PBC and osteoporosis and whether the relationship is independent of potential confounders. We performed bidirectional Mendelian randomization (MR) analyses to investigate the association between PBC (8021 cases and 16,489 controls) and osteoporosis in Europeans (the UK Biobank and FinnGen Consortium: 12,787 cases and 726,996 controls). The direct effect of PBC on osteoporosis was estimated using multivariable MR analyses. An independent replication was conducted in East Asians (PBC: 2495 cases and 4283 controls; osteoporosis: 9794 cases and 168,932 controls). Trans-ethnic meta-analysis was performed by pooling the MR estimates of Europeans and East Asians. Inverse-variance weighted analyses revealed that genetic liability to PBC was associated with a higher risk of osteoporosis in Europeans (OR, 1.040; 95% CI, 1.016-1.064; P = 0.001). Furthermore, the causal effect of PBC on osteoporosis persisted after adjusting for BMI, calcium, lipidemic traits, and sex hormones. The causal relationship was further validated in the East Asians (OR, 1.059; 95% CI, 1.023-1.096; P = 0.001). Trans-ethnic meta-analysis confirmed that PBC conferred increased risk on osteoporosis (OR, 1.045; 95% CI, 1.025-1.067; P = 8.17 × 10-6). Our data supports a causal effect of PBC on osteoporosis, and the causality is independent of BMI, calcium, triglycerides, and several sex hormones.
摘要：
骨质疏松是许多自身免疫性疾病的主要临床问题。包括原发性胆汁性胆管炎（PBC），最常见的自身免疫性肝病。骨质疏松是骨折和相关死亡率的主要原因。然而,目前尚不清楚PBC是否对骨质疏松症具有增加风险的因果关系.在这里，我们旨在调查PBC与骨质疏松症之间的因果关系,以及这种关系是否独立于潜在的混杂因素.我们进行了双向孟德尔随机化（MR）分析，以调查PBC（8021例和16,489例对照）与欧洲人骨质疏松症（英国生物银行和FinnGen联盟：12,787例和726,996例对照）之间的关联。使用多变量MR分析估计PBC对骨质疏松症的直接影响。在东亚人中进行了独立复制（PBC：2495例和4283例对照；骨质疏松症：9794例和168,932例对照）。跨种族荟萃分析是通过汇集欧洲人和东亚人的MR估计值进行的。逆方差加权分析显示，PBC的遗传倾向与欧洲人骨质疏松症的高风险相关(OR，1.040；95%CI，1.016-1.064；P=0.001）。此外，调整BMI后，PBC对骨质疏松症的因果关系仍然存在，钙，血脂性状，和性激素。因果关系在东亚人(OR，1.059；95%CI，1.023-1.096；P=0.001）。跨种族荟萃分析证实，PBC增加了骨质疏松症的风险(OR，1.045；95%CI，1.025-1.067；P=8.17×10-6）。我们的数据支持PBC对骨质疏松症的因果效应，因果关系与BMI无关，钙，甘油三酯，和几种性激素。
