基于孟德尔随机化方法探讨炎症性肠病与骨质疏松性骨折的因果关系

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	陈尚桐1
	陈跃平2
	宋世雷1
	黄川洪1

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Abstract： Objective： To investigate the causal relationship between inflammatory bowel disease and osteoporotic fracture by using the two-sample Mendelian randomization (MR) method. Methods: The pooled data from GenomeWide Association Studies (GWAS) were analyzed. Samples from Crohn′s disease and ulcerative colitis were selected for further analysis, where GWAS summary data for Crohn′s disease and ulcerative colitis were obtained from the European IEU database, 20 883 for Crohn′s disease, 47 745 for ulcerative colitis, and GWAS summary data for osteoporotic fractures from the FinnGen database, 173 619. Single nucleotide polymorphisms (SNPs), which are closely associated with Crohn′s disease and ulcerative colitis, were used as instrumental variables (IVs), and the inverse variance weighting method (IVW), the MR-Egger regression method, the Weighted Median method (WME), Simple Mode method and the Weighted Mode method were used to evaluate the causal relationship by means of odds ratio (OR). The Cochran Q heterogeneity test was performed by IVW and MR-Egger method, horizontal pleiotropy analysis by MR_pleiotropy_test function and MR PRESSO pleiotropy test, sensitivity analysis by MR_leaveoneout_plot function, and F values were calculated to evaluate the presence of weak IVs bias. Results: A total of 52 SNPs closely related to Crohn′s disease were obtained as IVs, IVW result ［OR(95%CI): 1.12(1.03-1.22), P=0.006］, WME result ［OR(95%CI) 1.15(1.01-1.32), P=0.02］, MREgger results ［OR(95%CI) 1.16(0.94-1.44), P=0.15］. Simple Mode results ［OR(95%CI): 1.15(0.88-1.50), P=0.28］ and Weighted Mode results ［OR(95%CI): 1.16(0.97-1.39), P=0.10］ suggested a positive causal relationship between Crohn′s disease and osteoporotic fracture. In total, 88 SNPs closely associated with ulcerative colitis were obtained as IVs, IVW result ［OR(95%CI) 1.15(1.03-1.28), P=0.009］, MREgger result ［OR(95%CI): 1.35(1.03-1.75), P=0.02］, WME result ［OR(95%CI): 1.18(1.01-1.37), P=0.02］, Simple Mode result ［OR(95%CI): 1.15(0.86-1.55), P=0.32］ and Weighted Mode results ［OR(95%CI): 1.19(0.96-1.47), P=0.10］ suggested a positive causal relationship between ulcerative colitis and osteoporotic fracture. The results of the heterogeneity test in Crohn′s disease-osteoporotic fractures were P=0.55 and P=0.52, respectively, suggesting the absence of heterogeneity. The MR_pleiotropy_test function result was P=0.69, and the MR PRESSO method result was P=0.55, indicating the absence of pleiotropy, and the sensitivity analysis showed stable results. The heterogeneity tests of ulcerative colitis-osteoporotic fractures were P=0.23 and P=0.25, respectively, suggesting the absence of heterogeneity. The MR_pleiotropy_test function result was P=0.20, and the MR PRESSO method result was P=0.24, indicating the absence of pleiotropy, and the sensitivity analysis showed stable results. All F values were greater than 10, suggesting that there was no weak IVs bias. Conclusion: Inflammatory bowel disease may increase the risk of osteoporotic fractures.

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收稿日期: 2023-07-11

基金资助: 国家自然科学基金资助项目(81960803)；广西壮族自治区医疗卫生临床重点学科急诊医学科（项目文号：桂卫医发{2021}8号）；广西临床重点专科（创伤外科）建设项目（项目文号：桂卫医发{2021}17号）；广西中医药大学A类“桂派中医药传承创新团队”（合同编号：2022A004）

通讯作者: 陈跃平（通讯作者），教授，主任医师，博士生导师，E-mail： chenyueping007@126.com

作者简介: 陈尚桐（1998—），男，硕士研究生

引用本文:

陈尚桐1，陈跃平2，宋世雷1，黄川洪1. 基于孟德尔随机化方法探讨炎症性肠病与骨质疏松性骨折的因果关系[J]. 江苏大学学报:医学版, 2024, 24(01): 67-73. CHEN Shangtong1, CHEN Yueping2, SONG Shilei1, HUANG Chuanhong1. The causal relationship between inflammatory bowel disease and osteoporosis fracture based on a Mendelian randomization

. Journal of Jiangsu University(Medicine Edition), 2024, 24(01): 67-73.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2024/V24/I01/67

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