Vitamin D and Inflammatory Bowel Disease: Mendelian Randomization Analyses in the Copenhagen Studies and UK Biobank.

CONTEXT

Vitamin D may be a modifiable risk factor for inflammatory bowel disease (IBD).

OBJECTIVES

We tested the hypothesis that plasma 25-hydroxyvitamin D levels are causally associated with risk of Crohn disease (CD) and ulcerative colitis (UC).

DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: We used a Mendelian randomization design to study 120,013 individuals from the Copenhagen City Heart Study, the Copenhagen General Population Study, and a Copenhagen-based cohort of patients with IBD. Of these, 35,558 individuals had plasma 25-hydroxyvitamin D measurements available, and 115,110 were genotyped for rs7944926 and rs11234027 in DHCR7 and rs10741657 and rs12794714 in CYP2R1, all variants associated with plasma 25-hydroxyvitamin D levels. We identified 653 cases of CD and 1265 cases of UC, of which 58 and 113, respectively, had 25-hydroxyvitamin D measurements available. We also included genetic data from 408,455 individuals from the UK Biobank, including 1707 CD cases and 3147 UC cases.

MAIN OUTCOME MEASURE

Hazard ratios for higher plasma 25-hydroxyvitamin D levels.

RESULTS

The multivariable-adjusted hazard ratios for 10 nmol/L higher 25-hydroxyvitamin D level were 1.04 (95% CI: 0.93 to 1.16) for CD and 1.13 (95% CI: 1.06 to 1.21) for UC. A combined 25-hydroxyvitamin D allele score was associated with a 1.4-nmol/L increase in plasma 25-hydroxyvitamin D level and hazard ratios of 0.98 (95% CI: 0.94 to 1.03) for CD and 1.01 (95% CI: 0.97 to 1.05) for UC. Combining genetic data from the Copenhagen studies and the UK Biobank, genetically determined vitamin D did not appear to influence the risk of CD or UC.

CONCLUSIONS

Our results do not support a major role for vitamin D deficiency in the development of IBD.