DataSheet_1_Causal association between thyroid dysfunction and sepsis: a two-sample mendelian randomization study.docx

BackgroundThe causal association between thyroid dysfunction (including hyperthyroidism and hypothyroidism) and sepsis is controversial in previous studies. Therefore, we used Mendelian randomization (MR) to explore the causal association between hyperthyroidism or hypothyroidism and the susceptibility to four distinct subtypes of sepsis (streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis).MethodsIn our research, we conducted two-sample Mendelian randomization (MR) analyses utilizing publicly available genome-wide association studies (GWAS) data from Sakaue et al. and the Finnish database to investigate the potential causal associations between hyperthyroidism, hypothyroidism, and each of the four distinct subtypes of sepsis, in addition to reverse MR analyses of the positive results to examine the existence of reverse causality.ResultsGenetic hypothyroidism was causally related to the development of asthma-associated pneumonia or sepsis (ORIVW: 1.097, 95% CI: 1.024 to 1.174, P = 0.008); hypothyroidism was significantly associated with the development of other sepsis (ORIVW: 1.070, 95% CI: 1.028 to 1.115, P < 0.001). In addition, sensitivity analysis substantiated the robustness of these two MR findings, with no evidence of horizontal pleiotropy observed (P > 0.05). MR Egger regression analysis demonstrated no heterogeneity between instrumental variables (IVs). Inverse MR results confirmed no reverse causality between hypothyroidism and asthma-associated pneumonia or sepsis, or between hypothyroidism and other sepsis. The findings of this study also unveiled that there is no evidence of a causal link between hypothyroidism and the development of streptococcal sepsis or puerperal sepsis. Additionally, the research provided evidence indicating the absence of a causal relationship between hyperthyroidism and streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis.ConclusionsThis study identified a causal link between hypothyroidism and the occurrence of asthma-associated pneumonia or sepsis, and other sepsis, but not with the development of streptococcal sepsis and puerperal sepsis. Moreover, our findings did not reveal any causal association between hyperthyroidism and streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis.

背景：既往研究中，甲状腺功能异常（包括甲状腺功能亢进和甲状腺功能减退）与败血症之间的因果关联存在争议。因此，本研究采用孟德尔随机化（MR）方法，旨在探究甲状腺功能亢进或甲状腺功能减退与四种不同亚型败血症（链球菌败血症、产褥期败血症、哮喘相关性肺炎或败血症以及其他败血症）易感性的因果关联。方法：本研究进行了两项样本孟德尔随机化（MR）分析，利用公开的全基因组关联研究（GWAS）数据，包括来自Sakaue等人的数据以及芬兰数据库的数据，以研究甲状腺功能亢进、甲状腺功能减退与四种不同亚型败血症之间潜在的因果关联，并进一步对阳性结果进行反向MR分析，以检验是否存在反向因果关系。结果：遗传性甲状腺功能减退与哮喘相关性肺炎或败血症的发生具有因果关联（ORIVW：1.097，95% CI：1.024至1.174，P = 0.008）；甲状腺功能减退与其他败血症的发生显著相关（ORIVW：1.070，95% CI：1.028至1.115，P < 0.001）。此外，敏感性分析证实了这两项MR发现的稳健性，未观察到水平多效性的证据（P > 0.05）。Egger回归分析显示，工具变量（IVs）之间不存在异质性。反向MR结果表明，甲状腺功能减退与哮喘相关性肺炎或败血症，以及甲状腺功能减退与其他败血症之间不存在反向因果关系。本研究的结果还揭示了甲状腺功能减退与链球菌败血症或产褥期败血症之间不存在因果联系。此外，研究提供了证据，表明甲状腺功能亢进与链球菌败血症、产褥期败血症、哮喘相关性肺炎或败血症以及其他败血症之间不存在因果关联。结论：本研究确认了甲状腺功能减退与哮喘相关性肺炎或败血症，以及其他败血症之间的因果关联，但并非与链球菌败血症和产褥期败血症的发生有关。此外，本研究未发现甲状腺功能亢进与链球菌败血症、产褥期败血症、哮喘相关性肺炎或败血症以及其他败血症之间存在任何因果关联。