Vitamin D levels and susceptibility to asthma, elevated IgE levels 3 and atopic dermatitis: A Mendelian randomization study

Introduction: Low circulating vitamin D levels have been associated with risk of
asthma, atopic dermatitis and elevated total IgE. These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable.
Methods and Results: To control bias due to confounding and reverse causation we applied Mendelian randomization (MR) to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis or serum IgE levels. Using four single nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25OHD) levels in 33,996 individuals, we conducted MR studies to estimate the effect of lowered 25OHD on the risk of asthma (n=146,761), childhood onset asthma (n=15,008), atopic dermatitis (n=40,835) and IgE level (n=12,853) and tested MR assumptions in sensitivity analyses. None of the four 25OHD-lowering alleles were associated with asthma, atopic dermatitis or IgE levels (P-values ≥0.2). The MR odds ratio per standard deviation decrease in log transformed 25OHD was 1.03 (95% CI 0.90,1.19, P=0.63) for asthma, 0.95 (95% CI 0.69,1.31, P=0.76) for childhood-onset asthma, 1.12 (95% CI 0.92,1.37, P=0.27) for atopic dermatitis and the effect size on log-transformed IgE levels was -0.40 (95% CI -1.65, 0.85, P =0.53). These results persisted in sensitivity analyses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathways. The main limitations of this study are that the above results do not exclude an association between the studied outcomes and 1,25-dihydoxyvitamin D, the active form of vitamin D, the study was underpowered to detect effects smaller that an OR of 1.33 for childhood asthma, and the analyses were restricted to white populations of European ancestry
Conclusions: In this study, we found no evidence that genetically-determined reduction in 25OHD levels conferred an increased risk of asthma, atopic dermatitis or elevated total serum IgE, suggesting that efforts to increase vitamin D are unlikely to reduce risks of atopic disease.