收稿日期: 2023-11-28
网络出版日期: 2024-04-08
基金资助
国家自然科学基金面上项目(32171277);山东省自然科学基金青年项目(ZR2022QH104)
The relationship between ulcerative colitis and the risk of hypothyroidism： A two⁃mendelian randomization study
Received date: 2023-11-28
Online published: 2024-04-08
目的 运用两样本孟德尔随机化（two sample mendelian randomization， TSMR）评估溃疡性结肠炎（ulcerative colitis， UC）与甲状腺功能减退（hypothyroidism， HT）之间的双向因果关系。 方法 UC与HT相关的单核苷酸多态性位点（single nucleotide polymorphism， SNP）数据分别来自芬兰生物银行和IEU数据库，提取出与UC强相关的独立SNP作为工具变量，采用逆方差加权法（inverse variance weighted，IVW）、Egger回归法（MR-Egger）、中位数加权法（weighted median）评估UC与HT之间的因果关联，同时采用MR-PRESSO评估水平多效性及离群的SNP，Cochran′s Q检测及漏斗图（funnel test）评估SNPs中的异质性，留一法分析（leave one out）是否存在单个SNP能够影响因果评估的结果。 结果 筛选出4个与UC强相关关联的工具变量，IVW法提示UC和HT之间存在因果关系（OR = 0.975，95%CI：0.924 ~ 0.990，P = 0.011），Cochran Q检验Q = 2.566，P = 0.463，提示SNP之间不存在异质性。MR-Egger法（P = 0.523）和MR-PRESSO法（P = 0.548）均提示不存在水平多效性，反向TSMR的结果不支持反向因果关系。 结论 TSMR发现UC与HT之间存在负向因果关系。
花胤 , 王晓燕 , 王振 , 辛永宁 , 刘守胜 . 孟德尔随机化研究溃疡性结肠炎与甲状腺功能减退发生风险的因果关系[J]. 实用医学杂志, 2024 , 40(6) : 827 -832 . DOI: 10.3969/j.issn.1006-5725.2024.06.016
Objective To investigate assess the bidirectional causal relationship between ulcerative colitis （UC） and hypothyroidism using a two?sample Mendelian randomization （TSMR）. Methods Single nucleotide polymorphism （SNP） data relevant to UC and hypothyroidism were retrieved from the Finnish Biobank and the IEU database， respectively. Independent SNPs strongly associated with UC were selected as instrumental variables. Causal associations between UC and hypothyroidism were evaluated using the inverse variance weighted （IVW） method， MR?Egger regression， and weighted median estimator. Additionally， MR?PRESSO was employed to assess the horizontal pleiotropy and outlier SNPs. Cochran′s Q test and funnel plots were performed to evaluate the heterogeneity among the SNPs. A leave?one?out analysis was conducted to examine the influence of individual SNPs on causal assessments. Results Four instrumental variables strongly associated with UC were identified. The IVW method indicated a causal relationship between UC and hypothyroidism （OR = 0.975， 95% CI： 0.924 ~ 0.990， P = 0.011）. Cochran′s Q test yielded a Q statistic of 2.566 with a p?value of 0.463， suggesting no heterogeneity among the SNPs. Both MR?Egger （P = 0.523） and MR?PRESSO （P = 0.548） tests suggested the absence of horizontal pleiotropy. However， the results of the reverse TSMR did not support a reverse causal relationship. Conclusion The findings from the TSMR analysis reveal a negative causal relationship between UC and hypothyroidism.
Key words： ulcerative colitis; hypothyroidism; mendelian randomization
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