TY - JOUR

T1 - Vitamin D and Inflammatory Bowel Disease

T2 - Mendelian Randomization Analyses in the Copenhagen Studies and UK Biobank

AU - Lund-Nielsen, Josephine

AU - Vedel-Krogh, Signe

AU - Kobylecki, Camilla Jannie

AU - Brynskov, Jørn

AU - Afzal, Shoaib

AU - Nordestgaard, Børge G

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1210/jc.2018-00250

DO - 10.1210/jc.2018-00250

M3 - Journal article

C2 - 29947775

VL - 103

SP - 3267

EP - 3277

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 9

ER -