孟德尔随机化分析胆石症与原发性硬化性胆管炎因果关系研究*

doi:10.3969/j.issn.1672-5069.2024.06.016

实用肝脏病杂志 ›› 2024, Vol. 27 ›› Issue (6): 860-865.doi: 10.3969/j.issn.1672-5069.2024.06.016

孟德尔随机化分析胆石症与原发性硬化性胆管炎因果关系研究^*

高梦晗, 陈澜斓, 张宇宁

130012 长春市吉林大学第一医院医学出版中心(高梦晗);普外中心肝胆胰外一科(陈澜斓);器官再造与移植教育部重点实验室(张宇宁)

收稿日期:2024-05-11 出版日期:2024-11-10 发布日期:2024-11-07
作者简介:高梦晗,女,流行病学博士。E-mail: menghan_gao@jlu.edu.cn
基金资助:
^*中国科技期刊卓越行动计划选育高水平办刊人才子项目——青年人才支持项目(编号:2023ZZ0530197);吉林省医疗卫生人才专项 (编号:JLSWSRCZX2023-81);白求恩计划项目(编号:2024B03);移植免疫教育部重点实验室开放课题重点项目(编号:KFKTZD2206)

Mendelian randomization unveils causal relationship between cholelithiasis and primary sclerosing cholangitis

Gao Menghan, Chen Lanlan, Zhang Yuning

Medical Publishing Centre, First Hospital, Jilin University, Changchun 130012, Jilin Province, China

Received:2024-05-11 Online:2024-11-10 Published:2024-11-07

摘要/Abstract

摘要： 目的探索胆石症与原发性硬化性胆管炎(PSC)之间的因果关系。方法 PSC的汇总数据来自国际PSC遗传学研究组(IPSCSG)开展的PSC全基因组关联研究和芬兰生物银行最新(FinnGen R10)的PSC汇总数据,开展孟德尔随机化(MR)分析,首先提取和胆石症密切相关的遗传工具变量,然后采用逆方差加权(IVW)和中位数加权(WM)法估算胆石症与PSC的因果关系,最后再应用反向MR评估PSC是否能导致胆石症。结果正向MR分析发现,胆石症能升高PSC的发生风险(OR_IVW:1.379,95%CI: 1.052～1.807,P=0.020;OR_WM: 1.450,95%CI:1.014～2.074,P=0.042),并且该结论在芬兰生物银行中得到证实(OR_IVW:1.98995,%CI:1.517～2.610,P=6.76×10^-7; OR_WM:1.931,95%CI:1.302～2.865,P=0.001);反向MR研究发现PSC并不改变胆石症的发病风险(OR_IVW:1.008,95%CI:0.991～1.024,P=0.356)。结论经MR研究发现胆石症是PSC发生的重要风险因素,而反向因果关系不成立。

关键词: 原发性硬化性胆管炎, 胆石症, 孟德尔随机化, 病因研究

Abstract: Objective The aim of this study was to explore causal relationship between cholelithiasis and primary sclerosing cholangitis (PSC). Methods Materials of patients with PSC were retrieved from International PSC Genetics Research Group (IPSCSG) and Finnish Biobank (FinnGen R10), and Mendelian randomization (MR) analysis was conducted by integrating summary data of published genome-wide association studies. Genetic instruments closely associated with cholelithiasis were extracted, and then causal relationship between cholelithiasis and PSC was estimated by using inverse-variance weighted (IVW) and weighted median (WM) methods. Finally, reverse MR was applied to assess whether PSC could lead to altered risk of cholelithiasis. Results Forward MR analysis found that genetic susceptibility to cholelithiasis could increase the risk of PSC (OR_IVW: 1.379, 95%CI: 1.052-1.807, P=0.020; OR_WM: 1.450, 95%CI: 1.014-2.074, P=0.042), and this result was validated in the FinnGen (OR_IVW: 1.989, 95%CI: 1.517-2.610, P=6.76×10^-7; OR_WM: 1.931, 95%CI: 1.302-2.865, P=0.001); reverse MR analysis found that genetically-predicted PSC did not alter the risk of cholelithiasis (OR_IVW: 1.008, 95%CI: 0.991-1.024, P=0.356). Conclusion This MR study find cholelithiasis is an important risk factor for occurrence of PSC, and the reverse causality is not established.

Key words: Primary sclerosing cholangitis, Cholelithiasis, Mendelian randomization, Etiological research

高梦晗, 陈澜斓, 张宇宁. 孟德尔随机化分析胆石症与原发性硬化性胆管炎因果关系研究^*[J]. 实用肝脏病杂志, 2024, 27(6): 860-865.

Gao Menghan, Chen Lanlan, Zhang Yuning. Mendelian randomization unveils causal relationship between cholelithiasis and primary sclerosing cholangitis[J]. Journal of Practical Hepatology, 2024, 27(6): 860-865.

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孟德尔随机化分析胆石症与原发性硬化性胆管炎因果关系研究^*

Mendelian randomization unveils causal relationship between cholelithiasis and primary sclerosing cholangitis

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