Context: Thyroid dysfunction is associated with higher anemia prevalence, though causality remains unclear. Objective: To investigate a potential causal relationship between thyroid function and anemia. Design: Cross-sectional and Mendelian Randomization study Setting: Europeans from UK Biobank Participants: 445,482 participants, mean age 56.77 years (SD 8.0) and 54.2% were women. Self-reported clinical diagnosis of hypothyroidism was stated by 21,860 (4.9%); self-reported clinical diagnosis of hyperthyroidism by 3,431 (0.8%). Main Outcome Measure: Anemia, defined as hemoglobin level of <13 g/dL in men and <12 g/dL in women, was present in 18,717 (4.2%) participants. Results: In cross-sectional logistic regression analyses, self-reported clinical diagnoses of hypo- and hyperthyroidism were associated with higher odds of anemia (OR 1.12, 95%CI 1.05-1.19 and OR 1.09, 95%CI 0.91-1.30), though with wide confidence intervals for hyperthyroidism. Although we considered a possible non-linear relationship, we did not observe an association of higher or lower genetically-influenced thyrotropin (TSH) with anemia (versus middle tertile: OR lowest tertile 0.98, 95% CI 0.95-1.02; highest tertile 1.02, 95% CI 0.98-1.06), nor of genetically-influenced free thyroxine (fT4) with anemia. Individuals with genetic variants in the DIO3OS gene implicated in intracellular regulation of thyroid hormones had a higher anemia risk (OR 1.05, 95% CI 1.02-1.10); no association was observed with variants in DIO1 or DIO2 genes. Conclusions: While self-reported clinical diagnosis of hypothyroidism was associated with a higher prevalence of anemia, we did not found evidence supporting this association was causal. However, intracellular regulation of thyroid hormones might play a role in developing anemia.

中文翻译：

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甲状腺功能和贫血风险：英国生物银行的多变量调整和孟德尔随机化分析

背景：甲状腺功能障碍与较高的贫血患病率有关，但因果关系尚不清楚。目的：探讨甲状腺功能与贫血之间的潜在因果关系。设计：横断面和孟德尔随机化研究 设置：来自英国生物银行的欧洲人 参与者：445,482 名参与者，平均年龄 56.77 岁 (SD 8.0)，54.2% 是女性。21,860 人（4.9%）报告了甲状腺功能减退症的自我报告临床诊断；自我报告的甲亢临床诊断为 3,431 (0.8%)。主要结果指标： 18,717 名 (4.2%) 参与者出现贫血，定义为男性血红蛋白水平 <13 g/dL，女性血红蛋白水平 <12 g/dL。结果：在横断面逻辑回归分析中，自我报告的甲状腺功能减退和甲状腺功能亢进的临床诊断与较高的贫血几率相关（OR 1.12，95%CI 1.05-1.19 和 OR 1.09, 95%CI 0.91-1.30)，但甲亢的置信区间很宽。尽管我们考虑了可能的非线性关系，但我们没有观察到较高或较低的遗传影响促甲状腺激素 (TSH) 与贫血之间的关联（与中间三分位数相比：OR 最低三分位数 0.98，95% CI 0.95-1.02；最高三分位数 1.02， 95% CI 0.98-1.06)，也不是受遗传影响的游离甲状腺素 (fT4) 与贫血。具有与甲状腺激素细胞内调节有关的 DIO3OS 基因遗传变异的个体具有更高的贫血风险（OR 1.05，95% CI 1.02-1.10）；未观察到与 DIO1 或 DIO2 基因变异的关联。结论：虽然自我报告的甲状腺功能减退症的临床诊断与较高的贫血患病率有关，但我们没有发现支持这种关联的证据是因果关系。