PDF(Pubmed)
Abstract：
BACKGROUND: Some previous observational studies have linked deep venous thrombosis (DVT) to thyroid diseases; however, the findings were contradictory. This study aimed to investigate whether some common thyroid diseases can cause DVT using a two-sample Mendelian randomization (MR) approach.
METHODS: This two-sample MR study used single nucleotide polymorphisms (SNPs) identified by the FinnGen genome-wide association studies (GWAS) to be highly associated with some common thyroid diseases, including autoimmune hyperthyroidism (962 cases and 172,976 controls), subacute thyroiditis (418 cases and 187,684 controls), hypothyroidism (26,342 cases and 59,827 controls), and malignant neoplasm of the thyroid gland (989 cases and 217,803 controls. These SNPs were used as instruments. Outcome datasets for the GWAS on DVT (6,767 cases and 330,392 controls) were selected from the UK Biobank data, which was obtained from the Integrative Epidemiology Unit (IEU) open GWAS project. The inverse variance weighted (IVW), MR-Egger and weighted median methods were used to estimate the causal association between DVT and thyroid diseases. The Cochran\'s Q test was used to quantify the heterogeneity of the instrumental variables (IVs). MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO) was used to detect horizontal pleiotropy. When the causal relationship was significant, bidirectional MR analysis was performed to determine any reverse causal relationships between exposures and outcomes.
RESULTS: This MR study illustrated that autoimmune hyperthyroidism slightly increased the risk of DVT according to the IVW [odds ratio (OR) = 1.0009; p = 0.024] and weighted median methods [OR = 1.001; p = 0.028]. According to Cochran\'s Q test, there was no evidence of heterogeneity in IVs. Additionally, MR-PRESSO did not detect horizontal pleiotropy (p = 0.972). However, no association was observed between other thyroid diseases and DVT using the IVW, weighted median, and MR-Egger regression methods.
CONCLUSIONS: This study revealed that autoimmune hyperthyroidism may cause DVT; however, more evidence and larger sample sizes are required to draw more precise conclusions.
METHODS: This two-sample MR study used single nucleotide polymorphisms (SNPs) identified by the FinnGen genome-wide association studies (GWAS) to be highly associated with some common thyroid diseases, including autoimmune hyperthyroidism (962 cases and 172,976 controls), subacute thyroiditis (418 cases and 187,684 controls), hypothyroidism (26,342 cases and 59,827 controls), and malignant neoplasm of the thyroid gland (989 cases and 217,803 controls. These SNPs were used as instruments. Outcome datasets for the GWAS on DVT (6,767 cases and 330,392 controls) were selected from the UK Biobank data, which was obtained from the Integrative Epidemiology Unit (IEU) open GWAS project. The inverse variance weighted (IVW), MR-Egger and weighted median methods were used to estimate the causal association between DVT and thyroid diseases. The Cochran\'s Q test was used to quantify the heterogeneity of the instrumental variables (IVs). MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO) was used to detect horizontal pleiotropy. When the causal relationship was significant, bidirectional MR analysis was performed to determine any reverse causal relationships between exposures and outcomes.
RESULTS: This MR study illustrated that autoimmune hyperthyroidism slightly increased the risk of DVT according to the IVW [odds ratio (OR) = 1.0009; p = 0.024] and weighted median methods [OR = 1.001; p = 0.028]. According to Cochran\'s Q test, there was no evidence of heterogeneity in IVs. Additionally, MR-PRESSO did not detect horizontal pleiotropy (p = 0.972). However, no association was observed between other thyroid diseases and DVT using the IVW, weighted median, and MR-Egger regression methods.
CONCLUSIONS: This study revealed that autoimmune hyperthyroidism may cause DVT; however, more evidence and larger sample sizes are required to draw more precise conclusions.
摘要：
背景：以前的一些观察性研究已将深静脉血栓（DVT）与甲状腺疾病联系起来；然而，调查结果相互矛盾。本研究旨在通过双样本孟德尔随机化（MR）方法研究某些常见的甲状腺疾病是否会导致DVT。
方法：这项双样本MR研究使用了FinnGen全基因组关联研究（GWAS）鉴定的单核苷酸多态性（SNPs）与一些常见的甲状腺疾病高度相关，包括自身免疫性甲状腺功能亢进（962例和172,976例对照），亚急性甲状腺炎（418例和187,684例对照），甲状腺功能减退（26,342例，59,827例对照），和甲状腺恶性肿瘤（989例和217,803例对照。这些SNP用作工具。从英国生物库数据中选择了DVT上GWAS的结果数据集（6,767例和330,392例对照），这是从综合流行病学单位（IEU）开放GWAS项目获得的。逆方差加权(IVW)，使用MR-Egger和加权中位数方法来估计DVT与甲状腺疾病之间的因果关系。CochranQ检验用于量化工具变量(IVs)的异质性。使用MR多效性RESidualSum和异常值测试(MR-PRESSO)来检测水平多效性。当因果关系显著时，我们进行了双向MR分析,以确定暴露与结局之间的任何反向因果关系.
结果：这项MR研究表明，根据IVW[比值比（OR）=1.0009；p=0.024]和加权中位数方法[OR=1.001；p=0.028]，自身免疫性甲状腺功能亢进略微增加了DVT的风险。根据Cochran的Q检验,没有证据表明IVs存在异质性.此外,MR-PRESSO未检测到水平多效性(p=0.972)。然而,使用IVW未观察到其他甲状腺疾病与DVT之间的关联，加权中位数，和MR-Egger回归方法。
结论：这项研究揭示自身免疫性甲状腺功能亢进可能导致DVT；然而，需要更多的证据和更大的样本量来得出更精确的结论。
方法：这项双样本MR研究使用了FinnGen全基因组关联研究（GWAS）鉴定的单核苷酸多态性（SNPs）与一些常见的甲状腺疾病高度相关，包括自身免疫性甲状腺功能亢进（962例和172,976例对照），亚急性甲状腺炎（418例和187,684例对照），甲状腺功能减退（26,342例，59,827例对照），和甲状腺恶性肿瘤（989例和217,803例对照。这些SNP用作工具。从英国生物库数据中选择了DVT上GWAS的结果数据集（6,767例和330,392例对照），这是从综合流行病学单位（IEU）开放GWAS项目获得的。逆方差加权(IVW)，使用MR-Egger和加权中位数方法来估计DVT与甲状腺疾病之间的因果关系。CochranQ检验用于量化工具变量(IVs)的异质性。使用MR多效性RESidualSum和异常值测试(MR-PRESSO)来检测水平多效性。当因果关系显著时，我们进行了双向MR分析,以确定暴露与结局之间的任何反向因果关系.
结果：这项MR研究表明，根据IVW[比值比（OR）=1.0009；p=0.024]和加权中位数方法[OR=1.001；p=0.028]，自身免疫性甲状腺功能亢进略微增加了DVT的风险。根据Cochran的Q检验,没有证据表明IVs存在异质性.此外,MR-PRESSO未检测到水平多效性(p=0.972)。然而,使用IVW未观察到其他甲状腺疾病与DVT之间的关联，加权中位数，和MR-Egger回归方法。
结论：这项研究揭示自身免疫性甲状腺功能亢进可能导致DVT；然而，需要更多的证据和更大的样本量来得出更精确的结论。
