■先前的观察性流行病学研究表明,甲状腺功能与炎症性肠病(IBD)之间存在潜在关联。然而,调查结果仍然没有定论,这种关联是否是因果关系仍不确定。这项研究的目的是探讨甲状腺功能与IBD之间的因果关系。
■涉及甲状腺功能七项指标的全基因组关联研究(GWAS),IBD,分析41种细胞因子。进行了双向双样本孟德尔随机化(MR)和多变量MR,以检查甲状腺功能与IBD之间的因果关系,并探索潜在的关联机制。
■遗传确定的甲状腺功能减退症显着降低了CD的风险(比值比[OR]=0.761,95%CI:0.655-0.882,p<0.001)。发现遗传确定的参考范围TSH对IBD具有暗示性因果关系(OR=0.931,95%CI:0.888-0.976,p=0.003),(克罗恩病)CD(OR=0.915,95%CI:0.857-0.977,p=0.008),和溃疡性结肠炎(UC)(OR=0.910,95%CI:0.830-0.997,p=0.043)。在反向MR分析中,IBD和CD似乎都对fT3/fT4比值有提示因果效应(分别为OR=1.002,p=0.013和OR=1.001,p=0.015).在41种细胞因子中,甲状腺功能减退对干扰素诱导蛋白-10(IP-10)有显著影响(OR=1.465,95%CI:1.094-1.962,p=0.010).多变量MR结果显示,IP-10可能介导甲状腺功能减退症合并CD的因果效应。
■我们的结果表明,TSH水平升高可降低患CD的风险,与IP-10可能调解这种关联。这突出了垂体-甲状腺轴可以作为CD的潜在治疗策略。
UNASSIGNED: Previous observational epidemiological studies have suggested a potential association between thyroid function and inflammatory bowel disease (IBD). However, the findings remain inconclusive, and whether this association is causal remains uncertain. The objective of this study is to investigate the causal association between thyroid function and IBD.
UNASSIGNED: Genome-wide association studies (GWAS) involving seven indicators of thyroid function, IBD, and 41 cytokines were analyzed. Bidirectional two-sample Mendelian randomization (MR) and multivariable MR were conducted to examine the causal relationship between thyroid function and IBD and to explore the potential mechanisms underlying the associations.
UNASSIGNED: Genetically determined hypothyroidism significantly reduced the risk of CD (odds ratio [OR] = 0.761, 95% CI: 0.655-0.882, p < 0.001). Genetically determined reference-range TSH was found to have a suggestive causal effect on IBD (OR = 0.931, 95% CI: 0.888-0.976, p = 0.003), (Crohn disease) CD (OR = 0.915, 95% CI: 0.857-0.977, p = 0.008), and ulcerative colitis (UC) (OR =0.910, 95% CI: 0.830-0.997, p = 0.043). In reverse MR analysis, both IBD and CD appeared to have a suggestive causal effect on the fT3/fT4 ratio (OR = 1.002, p = 0.013 and OR = 1.001, p = 0.015, respectively). Among 41 cytokines, hypothyroidism had a significant impact on interferon-inducible protein-10 (IP-10) (OR = 1.465, 95% CI: 1.094-1.962, p = 0.010). The results of multivariable MR showed that IP-10 may mediate the causal effects of hypothyroidism with CD.
UNASSIGNED: Our results suggest that an elevated TSH level reduces the risk of CD, with IP-10 potentially mediating this association. This highlights the pituitary-thyroid axis could serve as a potential therapeutic strategy for CD.