Osteoporosis and Primary Biliary Cholangitis: A Trans-ethnic Mendelian Randomization Analysis.

IF 8.4 2区 医学 Q1 ALLERGY Clinical Reviews in Allergy & Immunology Pub Date : 2024-04-01 Epub Date: 2024-03-30 DOI:10.1007/s12016-024-08986-4
Yi Wu, Qiwei Qian, Qiaoyan Liu, Rui Wang, Xiting Pu, Yao Li, Huayang Zhang, Zhengrui You, Qi Miao, Xiao Xiao, Min Lian, Qixia Wang, Minoru Nakamura, M Eric Gershwin, Zhiqiang Li, Xiong Ma, Ruqi Tang
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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.

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骨质疏松症与原发性胆汁性胆管炎:跨种族孟德尔随机分析
骨质疏松症是许多自身免疫性疾病的主要临床问题,包括最常见的自身免疫性肝病--原发性胆汁性胆管炎(PBC)。骨质疏松症是导致骨折和相关死亡的主要原因。然而,目前仍不清楚原发性胆汁性胆管炎是否会增加骨质疏松症的风险。在此,我们旨在研究 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,研究欧洲人(英国生物库和芬兰基因联盟:12787 例病例和 726996 例对照)中 PBC(8021 例病例和 16489 例对照)与骨质疏松症之间的关系。使用多变量 MR 分析估算了 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 例病例和 4283 例对照;骨质疏松症:9794 例病例和 168932 例对照)。通过汇总欧洲人和东亚人的 MR 估计值,进行了跨种族荟萃分析。逆方差加权分析显示,欧洲人的 PBC 遗传易感性与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,在对体重指数、钙、血脂特征和性激素进行调整后,PBC 对骨质疏松症的因果关系仍然存在。这种因果关系在东亚人中得到了进一步验证(OR,1.059;95% CI,1.023-1.096;P = 0.001)。跨种族荟萃分析证实,PBC 会增加骨质疏松症的风险(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,而且这种因果关系与体重指数、钙、甘油三酯和几种性激素无关。
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来源期刊
CiteScore
22.30
自引率
1.10%
发文量
58
审稿时长
6-12 weeks
期刊介绍: Clinical Reviews in Allergy & Immunology is a scholarly journal that focuses on the advancement of clinical management in allergic and immunologic diseases. The journal publishes both scholarly reviews and experimental papers that address the current state of managing these diseases, placing new data into perspective. Each issue of the journal is dedicated to a specific theme of critical importance to allergists and immunologists, aiming to provide a comprehensive understanding of the subject matter for a wide readership. The journal is particularly helpful in explaining how novel data impacts clinical management, along with advancements such as standardized protocols for allergy skin testing and challenge procedures, as well as improved understanding of cell biology. Ultimately, the journal aims to contribute to the improvement of care and management for patients with immune-mediated diseases.
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