Department of Rheumatology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Department of Hematology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
Department of Rheumatology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Hum Immunol. 2024 Sep;85(5):110856. doi: 10.1016/j.humimm.2024.110856. Epub 2024 Jul 16.
Previous studies have shown that inflammatory bowel disease (IBD) is associated with osteoporosis (OP) and bone mineral density (BMD), but the underlying genetic mechanisms are unclear. Our study wanted to explore the genetic and causal relationship between IBD and OP.
Based on large-scale genome-wide association summary statistics and individual-level datasets (i.e., the UK Biobank), this study performed linkage disequilibrium score regression (LDSC), pleiotropic analysis under the composite null hypothesis (PLACO), and Mendelian randomization (MR) analyses to explore the genetic association, the pleiotropic genes and the causal relationship between IBD and BMD.
LDSC revealed significant genetic correlations between IBD and BMD (e.g., forearm BMD (rg = -0.3479, P = 0.019) and femoral neck BMD (rg = -0.1335, P = 0.0307). PLACO identified 14 overlapping pleiotropic loci, 1 shared risk gene (CDYL), and multiple shared pathways, revealing possible mechanisms for IBD and OP. MR analysis demonstrated a causal association between IBD and BMD.
Our study indicates that IBD may increase the risk of OP and reveals a complex genetic mechanism linking IBD and the risk of osteoporosis, which has important implications for diagnosing and treating IBD and OP.
既往研究表明炎症性肠病（IBD）与骨质疏松症（OP）和骨密度（BMD）相关，但潜在的遗传机制尚不清楚。本研究旨在探讨 IBD 和 OP 之间的遗传及因果关系。
本研究基于大规模全基因组关联汇总统计数据和个体水平数据集（即英国生物银行），采用连锁不平衡评分回归（LDSC）、复合零假设下的多效性分析（PLACO）和孟德尔随机化（MR）分析，探讨 IBD 和 BMD 之间的遗传关联、多效性基因和因果关系。
LDSC 结果显示 IBD 和 BMD 之间存在显著的遗传相关性（例如，前臂 BMD（rg=-0.3479，P=0.019）和股骨颈 BMD（rg=-0.1335，P=0.0307）。PLACO 鉴定出 14 个重叠的多效性位点、1 个共享风险基因（CDYL）和多个共享通路，揭示了 IBD 和 OP 之间可能的机制。MR 分析表明 IBD 和 BMD 之间存在因果关系。
本研究表明 IBD 可能增加 OP 的风险，并揭示了 IBD 和骨质疏松风险之间复杂的遗传机制，这对 IBD 和 OP 的诊断和治疗具有重要意义。
