Le-Tai Li, Jia-Jie Leng, Yu-Xiang Luo, Rong-Jia Liu, Zhuo-Xuan Song, Meng Ye, Zhen-Han Li, Zhen-Rui Cao, Ying-Jiu Jiang, Hong-Tao Tie
{"title":"甲状腺活动功能与冠状动脉粥样硬化关系的双向孟德尔随机化分析。","authors":"Le-Tai Li, Jia-Jie Leng, Yu-Xiang Luo, Rong-Jia Liu, Zhuo-Xuan Song, Meng Ye, Zhen-Han Li, Zhen-Rui Cao, Ying-Jiu Jiang, Hong-Tao Tie","doi":"10.31083/j.rcm2512453","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Coronary atherosclerosis serves as the primary pathological etiology underlying coronary artery disease (CAD). Thyroid hormones show potential as risk factors, aside from the main standard modifiable cardiovascular risk factors (SMuRFs). This research seeks to elucidate the link between thyroid activity and coronary atherosclerosis.</p><p><strong>Methods: </strong>Single nucleotide polymorphisms (SNPs) linked to hypothyroidism (N = 213,990), Graves' disease (GD) (N = 190,034), other hyperthyroidism types (N = 190,799), thyroid-stimulating hormone (TSH) (N = 271,040), free thyroxine (FT4) (N = 119,120), and coronary atherosclerosis (N = 360,950) were retrieved from the IEU OpenGWAS, Finngen R9, and ThyroidOmics Consortium databases. Following the application of strict criteria to eliminate linkage disequilibrium, palindromic sequences, and heterozygous alleles, a bidirectional Mendelian Randomization (MR) analysis was conducted between the thyroid gland and coronary atherosclerosis using inverse variance weighting (IVW), weighted median (WM), and MR-Egger techniques. For sensitivity analysis, Cochran's Q test, leave-one-out method, and MR-Egger regression analysis were employed.</p><p><strong>Results: </strong>The forward MR analysis indicates that genetic predispositions such as hypothyroidism (OR = 1.07; 95% CI 1.01-1.12; IVW-<i>p</i> = 0.021), Graves' disease (OR = 1.04; 95% CI 1.01-1.07; IVW-<i>p</i> = 0.002), and other forms of hyperthyroidism (OR = 1.05; 95% CI 1.01-1.10; IVW-<i>p</i> = 0.021) elevate the likelihood of developing coronary atherosclerosis. Additionally, no discernible evidence of a causality between FT4 or TSH, and coronary atherosclerosis (IVW-<i>p</i> > 0.05) was found. Coronary atherosclerosis is not related to increased risk of five thyroid function phenotypes in reverse MR analysis. The sensitivity analysis provided relatively reliable evidence to reinforce the validity of our findings.</p><p><strong>Conclusions: </strong>Our findings are an investigation of the causality between thyroid function and coronary atherosclerosis. This study pinpointed potential heart disease risks linked to coronary atherosclerosis and offered additional understanding for defining SMuRFs in CAD.</p>","PeriodicalId":20989,"journal":{"name":"Reviews in cardiovascular medicine","volume":"25 12","pages":"453"},"PeriodicalIF":1.9000,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683704/pdf/","citationCount":"0","resultStr":"{\"title\":\"A Two-Way Mendelian Randomization Analysis on the Link between Thyroid Activity Function and Coronary Atherosclerosis.\",\"authors\":\"Le-Tai Li, Jia-Jie Leng, Yu-Xiang Luo, Rong-Jia Liu, Zhuo-Xuan Song, Meng Ye, Zhen-Han Li, Zhen-Rui Cao, Ying-Jiu Jiang, Hong-Tao Tie\",\"doi\":\"10.31083/j.rcm2512453\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Coronary atherosclerosis serves as the primary pathological etiology underlying coronary artery disease (CAD). Thyroid hormones show potential as risk factors, aside from the main standard modifiable cardiovascular risk factors (SMuRFs). This research seeks to elucidate the link between thyroid activity and coronary atherosclerosis.</p><p><strong>Methods: </strong>Single nucleotide polymorphisms (SNPs) linked to hypothyroidism (N = 213,990), Graves' disease (GD) (N = 190,034), other hyperthyroidism types (N = 190,799), thyroid-stimulating hormone (TSH) (N = 271,040), free thyroxine (FT4) (N = 119,120), and coronary atherosclerosis (N = 360,950) were retrieved from the IEU OpenGWAS, Finngen R9, and ThyroidOmics Consortium databases. Following the application of strict criteria to eliminate linkage disequilibrium, palindromic sequences, and heterozygous alleles, a bidirectional Mendelian Randomization (MR) analysis was conducted between the thyroid gland and coronary atherosclerosis using inverse variance weighting (IVW), weighted median (WM), and MR-Egger techniques. For sensitivity analysis, Cochran's Q test, leave-one-out method, and MR-Egger regression analysis were employed.</p><p><strong>Results: </strong>The forward MR analysis indicates that genetic predispositions such as hypothyroidism (OR = 1.07; 95% CI 1.01-1.12; IVW-<i>p</i> = 0.021), Graves' disease (OR = 1.04; 95% CI 1.01-1.07; IVW-<i>p</i> = 0.002), and other forms of hyperthyroidism (OR = 1.05; 95% CI 1.01-1.10; IVW-<i>p</i> = 0.021) elevate the likelihood of developing coronary atherosclerosis. Additionally, no discernible evidence of a causality between FT4 or TSH, and coronary atherosclerosis (IVW-<i>p</i> > 0.05) was found. Coronary atherosclerosis is not related to increased risk of five thyroid function phenotypes in reverse MR analysis. The sensitivity analysis provided relatively reliable evidence to reinforce the validity of our findings.</p><p><strong>Conclusions: </strong>Our findings are an investigation of the causality between thyroid function and coronary atherosclerosis. This study pinpointed potential heart disease risks linked to coronary atherosclerosis and offered additional understanding for defining SMuRFs in CAD.</p>\",\"PeriodicalId\":20989,\"journal\":{\"name\":\"Reviews in cardiovascular medicine\",\"volume\":\"25 12\",\"pages\":\"453\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-12-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683704/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reviews in cardiovascular medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.31083/j.rcm2512453\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reviews in cardiovascular medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.31083/j.rcm2512453","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
A Two-Way Mendelian Randomization Analysis on the Link between Thyroid Activity Function and Coronary Atherosclerosis.
Introduction: Coronary atherosclerosis serves as the primary pathological etiology underlying coronary artery disease (CAD). Thyroid hormones show potential as risk factors, aside from the main standard modifiable cardiovascular risk factors (SMuRFs). This research seeks to elucidate the link between thyroid activity and coronary atherosclerosis.
Methods: Single nucleotide polymorphisms (SNPs) linked to hypothyroidism (N = 213,990), Graves' disease (GD) (N = 190,034), other hyperthyroidism types (N = 190,799), thyroid-stimulating hormone (TSH) (N = 271,040), free thyroxine (FT4) (N = 119,120), and coronary atherosclerosis (N = 360,950) were retrieved from the IEU OpenGWAS, Finngen R9, and ThyroidOmics Consortium databases. Following the application of strict criteria to eliminate linkage disequilibrium, palindromic sequences, and heterozygous alleles, a bidirectional Mendelian Randomization (MR) analysis was conducted between the thyroid gland and coronary atherosclerosis using inverse variance weighting (IVW), weighted median (WM), and MR-Egger techniques. For sensitivity analysis, Cochran's Q test, leave-one-out method, and MR-Egger regression analysis were employed.
Results: The forward MR analysis indicates that genetic predispositions such as hypothyroidism (OR = 1.07; 95% CI 1.01-1.12; IVW-p = 0.021), Graves' disease (OR = 1.04; 95% CI 1.01-1.07; IVW-p = 0.002), and other forms of hyperthyroidism (OR = 1.05; 95% CI 1.01-1.10; IVW-p = 0.021) elevate the likelihood of developing coronary atherosclerosis. Additionally, no discernible evidence of a causality between FT4 or TSH, and coronary atherosclerosis (IVW-p > 0.05) was found. Coronary atherosclerosis is not related to increased risk of five thyroid function phenotypes in reverse MR analysis. The sensitivity analysis provided relatively reliable evidence to reinforce the validity of our findings.
Conclusions: Our findings are an investigation of the causality between thyroid function and coronary atherosclerosis. This study pinpointed potential heart disease risks linked to coronary atherosclerosis and offered additional understanding for defining SMuRFs in CAD.
期刊介绍：
RCM is an international, peer-reviewed, open access journal. RCM publishes research articles, review papers and short communications on cardiovascular medicine as well as research on cardiovascular disease. We aim to provide a forum for publishing papers which explore the pathogenesis and promote the progression of cardiac and vascular diseases. We also seek to establish an interdisciplinary platform, focusing on translational issues, to facilitate the advancement of research, clinical treatment and diagnostic procedures. Heart surgery, cardiovascular imaging, risk factors and various clinical cardiac & vascular research will be considered.
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