Mendelian Randomization Study Investigating the Causal Relationship Between Thyroid Dysfunction and Cerebral Infarction
ABSTRACT BACKGROUND There is an association between thyroid dysfunction and cerebral infarction (CI), but the causality cannot be determined. A two‐sample two‐way Mendelian randomization (MR) study was conducted to assess the causal relationship between thyroid function and CI. METHODS We selected s...
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Wiley
2024-12-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.70188 |
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| author | Letai Li Jiajie Leng Haibing Xiong Zishan Deng Meng Ye Haiyan Wang Xin Guo Shi Zeng Haofeng Xiong Jianhong Huo |
| author_facet | Letai Li Jiajie Leng Haibing Xiong Zishan Deng Meng Ye Haiyan Wang Xin Guo Shi Zeng Haofeng Xiong Jianhong Huo |
| author_sort | Letai Li |
| collection | DOAJ |
| description | ABSTRACT BACKGROUND There is an association between thyroid dysfunction and cerebral infarction (CI), but the causality cannot be determined. A two‐sample two‐way Mendelian randomization (MR) study was conducted to assess the causal relationship between thyroid function and CI. METHODS We selected single‐nucleotide polymorphisms (SNPs) associated with five phenotypes, including CI from the UK Biobank (n = 361,194), hyperthyroidism from the IEU Open GWAS database (n = 484,598), hypothyroidism from the IEU Open GWAS database (n = 473,703), normal thyroid‐stimulating hormone (TSH) (n = 271,040), and normal free thyroxine (FT4) (n = 119,120) from the Thyroidomics Consortium database. For the forward MR analysis, the exposures were hyperthyroidism, hypothyroidism, TSH, and FT4. The inverse variance weighted (IVW) method, weighted median (WM), and MR‐Egger revealed the causality with CI. For the reverse MR analysis, CI was regarded as the exposure, and four thyroid function phenotypes were the outcomes. The sensitivity and heterogeneity test was assessed using Cochran's Q test, MR‐Egger regression, and leave‐one‐out analysis. RESULTS The MR analysis indicated that genetic susceptibility to hyperthyroidism increased the risk of CI (IVW‐OR = 1.070; 95% CI: 1.015–1.128; p = 0.003). In reverse MR, genetic susceptibility to RA is not associated with hyperthyroidism (IVW‐OR = 1.001; 95% CI: 1.000–1.001; p = 0.144). Any positive or reverse causal relationship between hypothyroidism, FT4, and TSH with CI could not be established. Sensitivity and heterogeneity test consolidated our findings. CONCLUSION The causality between CI and hyperthyroidism demonstrated patients with hyperthyroidism have a risk of genetic variants for CI. In the future, further studies are needed to fully explore their mechanisms of action. |
| format | Article |
| id | doaj-art-8c8f2cc1b5d54e46a3feea2dceca1eb9 |
| institution | DOAJ |
| issn | 2162-3279 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj-art-8c8f2cc1b5d54e46a3feea2dceca1eb92025-08-20T02:50:48ZengWileyBrain and Behavior2162-32792024-12-011412n/an/a10.1002/brb3.70188Mendelian Randomization Study Investigating the Causal Relationship Between Thyroid Dysfunction and Cerebral InfarctionLetai Li0Jiajie Leng1Haibing Xiong2Zishan Deng3Meng Ye4Haiyan Wang5Xin Guo6Shi Zeng7Haofeng Xiong8Jianhong Huo9The First Clinical College of Chongqing Medical University Chongqing ChinaDepartment of Cardiothoracic Surgery The First Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Neurosurgery Banan Hospital of Chongqing Medical University Chongqing ChinaThe First Clinical College of Chongqing Medical University Chongqing ChinaThe First Clinical College of Chongqing Medical University Chongqing ChinaThe First Clinical College of Chongqing Medical University Chongqing ChinaDepartment of Neurosurgery Banan Hospital of Chongqing Medical University Chongqing ChinaDepartment of Neurosurgery Banan Hospital of Chongqing Medical University Chongqing ChinaDepartment of Neurosurgery Banan Hospital of Chongqing Medical University Chongqing ChinaDepartment of Neurosurgery Banan Hospital of Chongqing Medical University Chongqing ChinaABSTRACT BACKGROUND There is an association between thyroid dysfunction and cerebral infarction (CI), but the causality cannot be determined. A two‐sample two‐way Mendelian randomization (MR) study was conducted to assess the causal relationship between thyroid function and CI. METHODS We selected single‐nucleotide polymorphisms (SNPs) associated with five phenotypes, including CI from the UK Biobank (n = 361,194), hyperthyroidism from the IEU Open GWAS database (n = 484,598), hypothyroidism from the IEU Open GWAS database (n = 473,703), normal thyroid‐stimulating hormone (TSH) (n = 271,040), and normal free thyroxine (FT4) (n = 119,120) from the Thyroidomics Consortium database. For the forward MR analysis, the exposures were hyperthyroidism, hypothyroidism, TSH, and FT4. The inverse variance weighted (IVW) method, weighted median (WM), and MR‐Egger revealed the causality with CI. For the reverse MR analysis, CI was regarded as the exposure, and four thyroid function phenotypes were the outcomes. The sensitivity and heterogeneity test was assessed using Cochran's Q test, MR‐Egger regression, and leave‐one‐out analysis. RESULTS The MR analysis indicated that genetic susceptibility to hyperthyroidism increased the risk of CI (IVW‐OR = 1.070; 95% CI: 1.015–1.128; p = 0.003). In reverse MR, genetic susceptibility to RA is not associated with hyperthyroidism (IVW‐OR = 1.001; 95% CI: 1.000–1.001; p = 0.144). Any positive or reverse causal relationship between hypothyroidism, FT4, and TSH with CI could not be established. Sensitivity and heterogeneity test consolidated our findings. CONCLUSION The causality between CI and hyperthyroidism demonstrated patients with hyperthyroidism have a risk of genetic variants for CI. In the future, further studies are needed to fully explore their mechanisms of action.https://doi.org/10.1002/brb3.70188cerebral infarctionhyperthyroidismMendelian randomization analysisthyroid dysfunction |
| spellingShingle | Letai Li Jiajie Leng Haibing Xiong Zishan Deng Meng Ye Haiyan Wang Xin Guo Shi Zeng Haofeng Xiong Jianhong Huo Mendelian Randomization Study Investigating the Causal Relationship Between Thyroid Dysfunction and Cerebral Infarction Brain and Behavior cerebral infarction hyperthyroidism Mendelian randomization analysis thyroid dysfunction |
| title | Mendelian Randomization Study Investigating the Causal Relationship Between Thyroid Dysfunction and Cerebral Infarction |
| title_full | Mendelian Randomization Study Investigating the Causal Relationship Between Thyroid Dysfunction and Cerebral Infarction |
| title_fullStr | Mendelian Randomization Study Investigating the Causal Relationship Between Thyroid Dysfunction and Cerebral Infarction |
| title_full_unstemmed | Mendelian Randomization Study Investigating the Causal Relationship Between Thyroid Dysfunction and Cerebral Infarction |
| title_short | Mendelian Randomization Study Investigating the Causal Relationship Between Thyroid Dysfunction and Cerebral Infarction |
| title_sort | mendelian randomization study investigating the causal relationship between thyroid dysfunction and cerebral infarction |
| topic | cerebral infarction hyperthyroidism Mendelian randomization analysis thyroid dysfunction |
| url | https://doi.org/10.1002/brb3.70188 |
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