Vitamin D Deficiency Is Associated with Increased Depression Risk in Obese Asthma.

BACKGROUND: Asthma is frequently accompanied by depression, yet whether vitamin D deficiency increases depression risk remains unclear. OBJECTIVE: To examine the association between serum 25-hydroxyvitamin D (25(OH)D) and depression in adults with asthma, with particular attention to the role of overweight/obesity, and to explore potential mechanisms using genetic and transcriptomic evidence. METHODS: Using NHANES 2007-2018 and 2021-2023, logistic regression was applied to assess associations between 25(OH)D strata and depression with stratification by BMI. Two-sample Mendelian randomization (MR) tested causal relationships among 25(OH)D, asthma, depression, and BMI. Transcriptomic differentially expressed genes were integrated with disease-related genes for pathway enrichment. RESULTS: A total of 4,890 adults with asthma were included. Lower 25(OH)D levels showed a graded association with depression risk. Compared with sufficient 25(OH)D(≥75nmol/L), insufficiency (50-74.9 nmol/L), mild deficiency (25-49.9 nmol/L), and severe deficiency (<25 nmol/L) were associated with approximately 40%, 73%, and 97% higher risks of depression (all P < 0.05). This association was observed only in the overweight/obese subgroup (OR = 1.46, 95% CI: 1.15-1.86),P-interaction=0.285. MR analyses did not support a genetic causal effect of 25(OH)D on asthma or depression, whereas BMI showed positive causal effects on both. Transcriptomic analysis identified 69 core candidate genes. enriched in the Th17/neutrophil axis. CONCLUSIONS: Vitamin D deficiency was associated with higher odds of depression in asthma, reaching significance only in the overweight/obese subgroup, although the interaction was not significant. This association may involve the Th17/neutrophil inflammatory axis rather than direct genetic causality, supporting attention to vitamin D status and mental health in patients with asthma who are overweight/obese.