No Causative Link Between Vitamin D Deficiency and Asthma

Published Dec. 31, 2016
Journal of Allergy and Clinical Immunology

In examining the distinction between correlation and causation, researchers found that, despite multiple studies demonstrating correlation, vitamin D deficiency does not cause pediatric asthma, nor asthma exacerbations.

Vitamin D deficiency is highly prevalent in asthma, the most common chronic childhood disease. Researchers had long hypothesized that it had a causative effect through regulation of airway reactivity, sensitivity to corticosteroids, or modulation of immune function.

It took a Mendelian randomization approach, and a team of researchers that included Erik Hysinger, MD, MS, to demonstrate that Vitamin D deficiency is not in the causal pathway. Instead, asthma predisposes children to low levels of vitamin D.

Hysinger joined our Division of Pulmonary Medicine following his fellowship at Children’s Hospital of Philadelphia, where he was a co-first author on the study. It was published Dec. 31, 2016, in the Journal of Allergy and Clinical Immunology.

“The primary finding that low 25(OH)D is not in the causal pathway of asthma or asthma exacerbations was entirely unclear to us prior to performing the study,” Hysinger says.

The study cohort included 12,842 children with asthma. Previous epidemiology studies revealed that vitamin D is inversely correlated with the risk of asthma, but supplementation with vitamin D did not improve asthma health.

“In fact,” Hysinger says, “these differing data, along with confusion in the field, were the primary reasons that we wanted to do the study.”

In recent years, researchers have increasingly used Mendelian randomization to examine causality when association studies show one factor that is largely determined by genetics could impact disease.

“It was very exciting to use a novel technique to further investigate and provide new insight into this relationship,” says Hysinger.

The figure above shows the study cohort structure for the Center for Applied Genomics, with 56,835 subjects overall. One analytical method was the Mendelian randomization approach (blue), an epidemiological method that utilizes measured variation in genes of known function to examine the possible disease cause-effect in non-experimental studies. The other method was observational cross-sectional analysis (pink), which involves data from a specific point in time collected from a population or subset. Vitamin D data from a genome-wide association study appears in green.

Click image to enlarge.

This table shows the association of asthma indices and the genetic risk score of children with vitamin D deficiency. (*) denotes uni-variate logistic regression; (†) denotes univariate ordinal logistic regression, and (‡) denotes univariate zero-inflated Poisson regression.

Click image to enlarge.

Citation

Hysinger EB, Roizen JD, Mentch FD, Vazquez L, Connolly JJ, Bradfield JP, Almoguera B, Sleiman PM, Allen JL, Levine MA, Hakonarson H. Mendelian randomization analysis demonstrates that low vitamin D is unlikely causative for pediatric asthma. J Allergy Clin Immunol. 2016 Dec;138(6):1747-1749.e4.