Common Genetic Variants Influence Circulating Vitamin D Levels in Inflammatory Bowel Diseases.

Background: The accuracy and utility of electronic health record (EHR)-derived phenotypes in replicating genotype-phenotype relationships have been infrequently examined. Low circulating vitamin D levels are associated with severe outcomes in inflammatory bowel disease (IBD); however, the genetic basis for vitamin D insufficiency in this population has not been examined previously.

Methods: We compared the accuracy of physician-assigned phenotypes in a large prospective IBD registry to that identified by an EHR algorithm incorporating codified and structured data. Genotyping for IBD risk alleles was performed on the Immunochip and a genetic risk score calculated and compared between EHR-defined patients and those in the registry. Additionally, 4 vitamin D risk alleles were genotyped and serum 25-hydroxy vitamin D [25(OH)D] levels compared across genotypes.

Results: A total of 1131 patients captured by our EHR algorithm were also included in our prospective registry (656 Crohn's disease, 475 ulcerative colitis). The overall genetic risk score for Crohn's disease (P = 0.13) and ulcerative colitis (P = 0.32) was similar between EHR-defined patients and a prospective registry. Three of the 4 vitamin D risk alleles were associated with low vitamin D levels in patients with IBD and contributed an additional 3% of the variance explained. Vitamin D genetic risk score did not predict normalization of vitamin D levels.

Conclusions: EHR cohorts form valuable data sources for examining genotype-phenotype relationships. Vitamin D risk alleles explain 3% of the variance in vitamin D levels in patients with IBD.