This cross-sectional study used NHANES 2007–2018 and 2021–2023 data to examine whether serum 25(OH)D levels are associated with depression risk in 4,890 adults with asthma, stratified by BMI, with Mendelian randomization (MR) and transcriptomic analyses to explore causal mechanisms.
Lower 25(OH)D had a graded association with depression: insufficiency (50–74.9 nmol/L), mild deficiency (25–49.9 nmol/L), and severe deficiency (<25 nmol/L) were linked to ~40%, ~73%, and ~97% higher depression risk vs. sufficiency (≥75 nmol/L). The association was significant only in overweight/obese adults (OR 1.46, 95% CI 1.15–1.86), but the interaction term was not significant (P-interaction = 0.285). MR found no genetic causal effect of vitamin D on asthma or depression; BMI showed causal effects on both.
- The interaction by BMI subgroup was not statistically significant (P = 0.285), limiting conclusions about effect modification. - Cross-sectional design prevents causal inference between vitamin D and depression. - NHANES relies on self-reported depression and asthma diagnoses, which may introduce misclassification.
In adults with asthma who are overweight or obese, low vitamin D levels are associated with meaningfully higher odds of depression — consider screening for both vitamin D deficiency and depression in this group. However, current evidence does not confirm a direct causal relationship, so vitamin D repletion as a depression treatment strategy in asthma remains unproven.
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