Jing-jia Wang, Zhenhuang Zhuang, Canqing Yu, Wen-yao Wang, Wenxiu Wang, Kuo Zhang, X. Meng, Jun Gao, Jian Tian, Ji-lin Zheng, Jie Yang, Tao Huang, Chunli Shao, Yifang Tang
{"title":"评估甲状腺功能与心脏代谢健康之间的因果关系:一项孟德尔随机研究","authors":"Jing-jia Wang, Zhenhuang Zhuang, Canqing Yu, Wen-yao Wang, Wenxiu Wang, Kuo Zhang, X. Meng, Jun Gao, Jian Tian, Ji-lin Zheng, Jie Yang, Tao Huang, Chunli Shao, Yifang Tang","doi":"10.11909/j.issn.1671-5411.2022.01.004","DOIUrl":null,"url":null,"abstract":"BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism. However, the causal relationship of thyroid function and cardiometabolic health remains partly unknown. METHODS The Mendelian randomization (MR) was used to test genetic, potentially causal relationships between instrumental variables and cardiometabolic traits. Genetic variants of free thyroxine (FT4) and thyrotropin (TSH) levels within the reference range were used as instrumental variables. Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen, CARDIoGRAM and CARDIoGRAMplusC4D, CHARGE, and MEGASTROKE. This study was conducted using summary statistic data from large, previously described cohorts. Association between thyroid function and essential hypertension (EHTN), secondary hypertension (SHTN), hyperlipidemia (HPL), type 2 diabetes mellitus (T2DM), ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), pulmonary heart disease (PHD), stroke, and non-rheumatic valve disease (NRVD) were examined. RESULTS Genetically predicted FT4 levels were associated with SHTN (odds ratio = 0.48; 95% CI = 0.04−0.82,P = 0.027), HPL (odds ratio = 0.67; 95% CI = 0.18−0.88,P = 0.023), T2DM (odds ratio = 0.80; 95% CI = 0.42−0.86,P = 0.005), IHD (odds ratio = 0.85; 95% CI = 0.49−0.98,P = 0.039), NRVD (odds ratio = 0.75; 95% CI = 0.27−0.97,P = 0.039). Additionally, genetically predicted TSH levels were associated with HF (odds ratio = 0.82; 95% CI = 0.68−0.99,P = 0.042), PHD (odds ratio = 0.75; 95% CI = 0.32−0.82,P = 0.006), stroke (odds ratio = 0.95; 95% CI = 0.81−0.97,P = 0.007). However, genetically predicted thyroid function traits were not associated with EHTN and MI. CONCLUSIONS Our study suggests FT4 and TSH are associated with cardiometabolic diseases, underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.","PeriodicalId":285674,"journal":{"name":"Journal of geriatric cardiology : JGC","volume":"103 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":"{\"title\":\"Assessment of causal direction between thyroid function and cardiometabolic health: a Mendelian randomization study\",\"authors\":\"Jing-jia Wang, Zhenhuang Zhuang, Canqing Yu, Wen-yao Wang, Wenxiu Wang, Kuo Zhang, X. Meng, Jun Gao, Jian Tian, Ji-lin Zheng, Jie Yang, Tao Huang, Chunli Shao, Yifang Tang\",\"doi\":\"10.11909/j.issn.1671-5411.2022.01.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism. However, the causal relationship of thyroid function and cardiometabolic health remains partly unknown. METHODS The Mendelian randomization (MR) was used to test genetic, potentially causal relationships between instrumental variables and cardiometabolic traits. Genetic variants of free thyroxine (FT4) and thyrotropin (TSH) levels within the reference range were used as instrumental variables. Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen, CARDIoGRAM and CARDIoGRAMplusC4D, CHARGE, and MEGASTROKE. This study was conducted using summary statistic data from large, previously described cohorts. Association between thyroid function and essential hypertension (EHTN), secondary hypertension (SHTN), hyperlipidemia (HPL), type 2 diabetes mellitus (T2DM), ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), pulmonary heart disease (PHD), stroke, and non-rheumatic valve disease (NRVD) were examined. RESULTS Genetically predicted FT4 levels were associated with SHTN (odds ratio = 0.48; 95% CI = 0.04−0.82,P = 0.027), HPL (odds ratio = 0.67; 95% CI = 0.18−0.88,P = 0.023), T2DM (odds ratio = 0.80; 95% CI = 0.42−0.86,P = 0.005), IHD (odds ratio = 0.85; 95% CI = 0.49−0.98,P = 0.039), NRVD (odds ratio = 0.75; 95% CI = 0.27−0.97,P = 0.039). Additionally, genetically predicted TSH levels were associated with HF (odds ratio = 0.82; 95% CI = 0.68−0.99,P = 0.042), PHD (odds ratio = 0.75; 95% CI = 0.32−0.82,P = 0.006), stroke (odds ratio = 0.95; 95% CI = 0.81−0.97,P = 0.007). However, genetically predicted thyroid function traits were not associated with EHTN and MI. CONCLUSIONS Our study suggests FT4 and TSH are associated with cardiometabolic diseases, underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.\",\"PeriodicalId\":285674,\"journal\":{\"name\":\"Journal of geriatric cardiology : JGC\",\"volume\":\"103 1\",\"pages\":\"0\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-01-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of geriatric cardiology : JGC\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.11909/j.issn.1671-5411.2022.01.004\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of geriatric cardiology : JGC","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.11909/j.issn.1671-5411.2022.01.004","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3
摘要
背景越来越多的证据表明，甲状腺激素参与了心血管代谢的过程。然而，甲状腺功能与心脏代谢健康的因果关系仍部分未知。方法采用孟德尔随机化(MR)来检验工具变量与心脏代谢性状之间的遗传关系和潜在因果关系。参考范围内游离甲状腺素(FT4)和促甲状腺素(TSH)水平的遗传变异作为工具变量。与心脏代谢疾病的遗传关联数据来自FinnGen、CARDIoGRAM和CARDIoGRAMplusC4D、CHARGE和MEGASTROKE的全基因组关联研究。本研究是利用先前描述的大型队列的汇总统计数据进行的。观察甲状腺功能与原发性高血压(EHTN)、继发性高血压(SHTN)、高脂血症(HPL)、2型糖尿病(T2DM)、缺血性心脏病(IHD)、心肌梗死(MI)、心力衰竭(HF)、肺心病(PHD)、脑卒中、非风湿性瓣膜病(NRVD)的关系。结果基因预测的FT4水平与SHTN相关(优势比= 0.48;95% CI = 0.04 ~ 0.82,P = 0.027)， HPL(优势比= 0.67;95% CI = 0.18−0.88,P = 0.023)， T2DM(优势比= 0.80;95% CI = 0.42 ~ 0.86,P = 0.005)， IHD(优势比= 0.85;95% CI = 0.49 ~ 0.98,P = 0.039)， NRVD(优势比= 0.75;95% ci = 0.27 ~ 0.97, p = 0.039)。此外，基因预测的TSH水平与HF相关(优势比= 0.82;95% CI = 0.68 ~ 0.99,P = 0.042)， PHD(优势比= 0.75;95% CI = 0.32 ~ 0.82,P = 0.006)，卒中(优势比= 0.95;95% ci = 0.81−0.97,p = 0.007)。然而，遗传预测的甲状腺功能特征与EHTN和MI无关。结论我们的研究表明FT4和TSH与心脏代谢疾病相关，强调了垂体-甲状腺-心脏轴在心脏代谢健康易感性中的重要性。
Assessment of causal direction between thyroid function and cardiometabolic health: a Mendelian randomization study
BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism. However, the causal relationship of thyroid function and cardiometabolic health remains partly unknown. METHODS The Mendelian randomization (MR) was used to test genetic, potentially causal relationships between instrumental variables and cardiometabolic traits. Genetic variants of free thyroxine (FT4) and thyrotropin (TSH) levels within the reference range were used as instrumental variables. Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen, CARDIoGRAM and CARDIoGRAMplusC4D, CHARGE, and MEGASTROKE. This study was conducted using summary statistic data from large, previously described cohorts. Association between thyroid function and essential hypertension (EHTN), secondary hypertension (SHTN), hyperlipidemia (HPL), type 2 diabetes mellitus (T2DM), ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), pulmonary heart disease (PHD), stroke, and non-rheumatic valve disease (NRVD) were examined. RESULTS Genetically predicted FT4 levels were associated with SHTN (odds ratio = 0.48; 95% CI = 0.04−0.82,P = 0.027), HPL (odds ratio = 0.67; 95% CI = 0.18−0.88,P = 0.023), T2DM (odds ratio = 0.80; 95% CI = 0.42−0.86,P = 0.005), IHD (odds ratio = 0.85; 95% CI = 0.49−0.98,P = 0.039), NRVD (odds ratio = 0.75; 95% CI = 0.27−0.97,P = 0.039). Additionally, genetically predicted TSH levels were associated with HF (odds ratio = 0.82; 95% CI = 0.68−0.99,P = 0.042), PHD (odds ratio = 0.75; 95% CI = 0.32−0.82,P = 0.006), stroke (odds ratio = 0.95; 95% CI = 0.81−0.97,P = 0.007). However, genetically predicted thyroid function traits were not associated with EHTN and MI. CONCLUSIONS Our study suggests FT4 and TSH are associated with cardiometabolic diseases, underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.
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