Thyroid function and risk of anemia: a multivariable-adjusted and Mendelian Randomization analysis in the UK Biobank

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.