Abstract：
BACKGROUND: The association between hypothyroidism and stroke remains controversial and the association between hypothyroidism and stroke subtypes has not been satisfactorily researched. This study aimed to explore the causal effect of hypothyroidism on the risk of stroke and its subtypes by Mendelian randomization (MR) analysis.
METHODS: Single nucleotide polymorphisms (SNPs) were selected from published genome-wide association studies (GWAS) meta-analysis as instrumental variables (IVs) for hypothyroidism. As outcomes, summary GWAS data for stroke and its subtypes were obtained from two other large GWAS meta-analyses, including any stroke (AS), any ischemic stroke (AIS), large vessel stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), and intracranial hemorrhage (ICH). Univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) were used to assess the causal effect of hypothyroidism on stroke and its subtypes.
RESULTS: In UVMR, genetically predicted hypothyroidism was significantly associated with LAS (OR = 1.14, 95CI = 1.02-1.27) and SVS (OR = 1.14, 95CI = 1.04-1.25), but not with AS, AIS, CES, and ICH. The results of the MVMR showed that after adjusting for smoking, alcohol consumption, hypertension, diabetes, low-density lipoprotein cholesterol (LDL-c), and body mass index (BMI), the causal association between hypothyroidism and SVS remained significant, while the association between hypothyroidism and LAS became nonsignificant.
CONCLUSIONS: Hypothyroidism is causally associated with risk for LAS and SVS, but not for other stroke subtypes. Hypothyroidism may be an independent risk factor for SVS, and vascular risk factors play an important role in hypothyroidism causing LAS.
METHODS: Single nucleotide polymorphisms (SNPs) were selected from published genome-wide association studies (GWAS) meta-analysis as instrumental variables (IVs) for hypothyroidism. As outcomes, summary GWAS data for stroke and its subtypes were obtained from two other large GWAS meta-analyses, including any stroke (AS), any ischemic stroke (AIS), large vessel stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), and intracranial hemorrhage (ICH). Univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) were used to assess the causal effect of hypothyroidism on stroke and its subtypes.
RESULTS: In UVMR, genetically predicted hypothyroidism was significantly associated with LAS (OR = 1.14, 95CI = 1.02-1.27) and SVS (OR = 1.14, 95CI = 1.04-1.25), but not with AS, AIS, CES, and ICH. The results of the MVMR showed that after adjusting for smoking, alcohol consumption, hypertension, diabetes, low-density lipoprotein cholesterol (LDL-c), and body mass index (BMI), the causal association between hypothyroidism and SVS remained significant, while the association between hypothyroidism and LAS became nonsignificant.
CONCLUSIONS: Hypothyroidism is causally associated with risk for LAS and SVS, but not for other stroke subtypes. Hypothyroidism may be an independent risk factor for SVS, and vascular risk factors play an important role in hypothyroidism causing LAS.
摘要：
背景：甲状腺功能减退与卒中之间的关系仍存在争议，甲状腺功能减退与卒中亚型之间的关系尚未得到令人满意的研究。本研究旨在通过孟德尔随机化（MR）分析探讨甲状腺功能减退症对卒中风险及其亚型的因果关系。
方法：从已发表的全基因组关联研究（GWAS）荟萃分析中选择单核苷酸多态性（SNPs）作为甲状腺功能减退症的工具变量（IVs）。作为结果，卒中及其亚型的汇总GWAS数据来自另外两项大型GWAS荟萃分析,包括任何行程（AS），任何缺血性卒中（AIS），大血管冲程(LAS)，心源性栓塞性中风（CES），小血管冲程(SVS)，颅内出血（ICH）。单因素孟德尔随机化（UVMR）和多因素孟德尔随机化（MVMR）用于评估甲状腺功能减退对中风及其亚型的因果影响。
结果：在UVMR中，遗传预测的甲状腺功能减退症与LAS（OR=1.14，95CI=1.02-1.27）和SVS（OR=1.14，95CI=1.04-1.25）显着相关，但不是AS，AIS,CES,和ICH。MVMR的结果表明，在调整吸烟后，酒精消费,高血压,糖尿病,低密度脂蛋白胆固醇（LDL-c），和体重指数（BMI），甲状腺功能减退症和SVS之间的因果关系仍然显著，而甲状腺功能减退症和LAS之间的关联变得不显著。
结论：甲状腺功能减退与LAS和SVS的风险有因果关系，但不适用于其他中风亚型。甲状腺功能减退可能是SVS的独立危险因素,血管危险因素在甲状腺功能减退症引起的LAS中起重要作用。
方法：从已发表的全基因组关联研究（GWAS）荟萃分析中选择单核苷酸多态性（SNPs）作为甲状腺功能减退症的工具变量（IVs）。作为结果，卒中及其亚型的汇总GWAS数据来自另外两项大型GWAS荟萃分析,包括任何行程（AS），任何缺血性卒中（AIS），大血管冲程(LAS)，心源性栓塞性中风（CES），小血管冲程(SVS)，颅内出血（ICH）。单因素孟德尔随机化（UVMR）和多因素孟德尔随机化（MVMR）用于评估甲状腺功能减退对中风及其亚型的因果影响。
结果：在UVMR中，遗传预测的甲状腺功能减退症与LAS（OR=1.14，95CI=1.02-1.27）和SVS（OR=1.14，95CI=1.04-1.25）显着相关，但不是AS，AIS,CES,和ICH。MVMR的结果表明，在调整吸烟后，酒精消费,高血压,糖尿病,低密度脂蛋白胆固醇（LDL-c），和体重指数（BMI），甲状腺功能减退症和SVS之间的因果关系仍然显著，而甲状腺功能减退症和LAS之间的关联变得不显著。
结论：甲状腺功能减退与LAS和SVS的风险有因果关系，但不适用于其他中风亚型。甲状腺功能减退可能是SVS的独立危险因素,血管危险因素在甲状腺功能减退症引起的LAS中起重要作用。
