PDF(Pubmed)
Abstract：
BACKGROUND: Numerous organs, including the thyroid gland, depend on vitamin D to function normally. Insufficient levels of serum 25-hydroxyvitamin D [25(OH)D] are seen as a potential factor contributing to the emergence of several thyroid disorders, however, the causal relationship remains unclear. Here we use a Mendelian randomization (MR) approach to investigate the causal effect of serum 25(OH)D concentration on the indicators of thyroid function.
METHODS: We conducted a two-sample MR analysis utilizing summary data from the most extensive genome-wide association studies (GWAS) of serum 25(OH)D concentration (n = 443,734 and 417,580), thyroid-stimulating hormone (TSH, n = 271,040), free thyroxine (fT4, n = 119,120), free triiodothyronine (fT3, n = 59,061), total triiodothyronine (TT3, n = 15,829), as well as thyroid peroxidase antibody levels and positivity (TPOAb, n = 12,353 and n = 18,297), low TSH (n = 153,241), high TSH (n = 141,549), autoimmune hypothyroidism (n = 287,247) and autoimmune hyperthyroidism (n = 257,552). The primary analysis was conducted using the multiplicative random-effects inverse variance weighted (IVW) method. The weighted mode, weighted median, MR-Egger, MR-PRESSO, and Causal Analysis Using Summary Effect estimates (CAUSE) were used in the sensitivity analysis.
RESULTS: The IVW, as well as MR Egger and CAUSE analysis, showed a suggestive causal effect of 25(OH)D concentration on high TSH. Each 1 SD increase in serum 25(OH)D concentration was associated with a 12% decrease in the risk of high TSH (p = 0.02). Additionally, in the MR Egger and CAUSE analysis, we found a suggestive causal effect of 25(OH)D concentration on autoimmune hypothyroidism. Specifically, each 1 SD increase in serum 25(OH)D concentration was associated with a 16.34% decrease in the risk of autoimmune hypothyroidism (p = 0.02).
CONCLUSIONS: Our results support a suggestive causal effect which was negative in direction across all methods used, meaning that higher genetically predicted vitamin D concentration possibly lowers the odds of having high TSH or autoimmune hypothyroidism. Other thyroid parameters were not causally influenced by vitamin D serum concentration.
METHODS: We conducted a two-sample MR analysis utilizing summary data from the most extensive genome-wide association studies (GWAS) of serum 25(OH)D concentration (n = 443,734 and 417,580), thyroid-stimulating hormone (TSH, n = 271,040), free thyroxine (fT4, n = 119,120), free triiodothyronine (fT3, n = 59,061), total triiodothyronine (TT3, n = 15,829), as well as thyroid peroxidase antibody levels and positivity (TPOAb, n = 12,353 and n = 18,297), low TSH (n = 153,241), high TSH (n = 141,549), autoimmune hypothyroidism (n = 287,247) and autoimmune hyperthyroidism (n = 257,552). The primary analysis was conducted using the multiplicative random-effects inverse variance weighted (IVW) method. The weighted mode, weighted median, MR-Egger, MR-PRESSO, and Causal Analysis Using Summary Effect estimates (CAUSE) were used in the sensitivity analysis.
RESULTS: The IVW, as well as MR Egger and CAUSE analysis, showed a suggestive causal effect of 25(OH)D concentration on high TSH. Each 1 SD increase in serum 25(OH)D concentration was associated with a 12% decrease in the risk of high TSH (p = 0.02). Additionally, in the MR Egger and CAUSE analysis, we found a suggestive causal effect of 25(OH)D concentration on autoimmune hypothyroidism. Specifically, each 1 SD increase in serum 25(OH)D concentration was associated with a 16.34% decrease in the risk of autoimmune hypothyroidism (p = 0.02).
CONCLUSIONS: Our results support a suggestive causal effect which was negative in direction across all methods used, meaning that higher genetically predicted vitamin D concentration possibly lowers the odds of having high TSH or autoimmune hypothyroidism. Other thyroid parameters were not causally influenced by vitamin D serum concentration.
摘要：
背景：众多器官，包括甲状腺,依赖维生素D正常运作。血清25-羟维生素D[25（OH）D]水平不足被视为导致几种甲状腺疾病出现的潜在因素。然而,因果关系尚不清楚.在这里，我们使用孟德尔随机化（MR）方法来研究血清25（OH）D浓度对甲状腺功能指标的因果关系。
方法：我们利用来自最广泛的全基因组关联研究（GWAS）的血清25（OH）D浓度的汇总数据（n=443,734和417,580）进行了双样本MR分析。促甲状腺激素（TSH，n=271,040),游离甲状腺素（fT4，n=119,120），游离三碘甲状腺原氨酸（fT3，n=59,061），总三碘甲状腺原氨酸（TT3，n=15,829），以及甲状腺过氧化物酶抗体水平和阳性(TPOAb，n=12,353和n=18,297)，低TSH（n=153,241），高TSH（n=141,549），自身免疫性甲状腺功能减退（n=287,247）和自身免疫性甲状腺功能亢进（n=257,552）。主要分析是使用乘法随机效应逆方差加权（IVW）方法进行的。加权模式，加权中位数，MR-Egger,MR-PRESSO,敏感性分析中使用了使用汇总效应估计(CAUSE)的因果分析。
结果：IVW，以及MREgger和原因分析，显示25（OH）D浓度对高TSH的暗示因果关系。血清25（OH）D浓度每增加1SD，与高TSH风险降低12％相关（p=0.02）。此外,在MREgger和原因分析中，我们发现25(OH)D浓度对自身免疫性甲状腺功能减退症有提示因果关系.具体来说,血清25(OH)D浓度每增加1SD,与自身免疫性甲状腺功能减退症风险降低16.34%相关(p=0.02).
结论：我们的结果支持一种暗示性因果效应，该效应在所有使用的方法中都是负面的，这意味着较高的遗传预测的维生素D浓度可能会降低高TSH或自身免疫性甲状腺功能减退症的几率。其他甲状腺参数不受维生素D血清浓度的因果关系影响。
方法：我们利用来自最广泛的全基因组关联研究（GWAS）的血清25（OH）D浓度的汇总数据（n=443,734和417,580）进行了双样本MR分析。促甲状腺激素（TSH，n=271,040),游离甲状腺素（fT4，n=119,120），游离三碘甲状腺原氨酸（fT3，n=59,061），总三碘甲状腺原氨酸（TT3，n=15,829），以及甲状腺过氧化物酶抗体水平和阳性(TPOAb，n=12,353和n=18,297)，低TSH（n=153,241），高TSH（n=141,549），自身免疫性甲状腺功能减退（n=287,247）和自身免疫性甲状腺功能亢进（n=257,552）。主要分析是使用乘法随机效应逆方差加权（IVW）方法进行的。加权模式，加权中位数，MR-Egger,MR-PRESSO,敏感性分析中使用了使用汇总效应估计(CAUSE)的因果分析。
结果：IVW，以及MREgger和原因分析，显示25（OH）D浓度对高TSH的暗示因果关系。血清25（OH）D浓度每增加1SD，与高TSH风险降低12％相关（p=0.02）。此外,在MREgger和原因分析中，我们发现25(OH)D浓度对自身免疫性甲状腺功能减退症有提示因果关系.具体来说,血清25(OH)D浓度每增加1SD,与自身免疫性甲状腺功能减退症风险降低16.34%相关(p=0.02).
结论：我们的结果支持一种暗示性因果效应，该效应在所有使用的方法中都是负面的，这意味着较高的遗传预测的维生素D浓度可能会降低高TSH或自身免疫性甲状腺功能减退症的几率。其他甲状腺参数不受维生素D血清浓度的因果关系影响。
