title: Common Genetic Variants Influence Circulating Vitamin D Levels in Inflammatory Bowel Diseases.
abstract: 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.
authors.affiliation: *Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts; †Harvard Medical School, Boston, Massachusetts; ‡Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; §Research IS and Computing, Partners HealthCare, Charlestown, Massachusetts; ‖Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; ¶Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts; **i2b2 National Center for Biomedical Computing, Boston, Massachusetts; ††Division of Rheumatology, Allergy and Immunology, Brigham and Women's Hospital, Boston, Massachusetts; ‡‡Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts; §§Children's Hospital Boston, Boston, Massachusetts; and ‖‖Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Ashwin N
authors.initials: AN
authors.lastname: Ananthakrishnan
authors.forename: Andrew
authors.initials: A
authors.lastname: Cagan
authors.forename: Tianxi
authors.initials: T
authors.lastname: Cai
authors.forename: Vivian S
authors.initials: VS
authors.lastname: Gainer
authors.forename: Stanley Y
authors.initials: SY
authors.lastname: Shaw
authors.forename: Susanne
authors.initials: S
authors.lastname: Churchill
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
authors.forename: Shawn N
authors.initials: SN
authors.lastname: Murphy
authors.forename: Isaac
authors.initials: I
authors.lastname: Kohane
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Liao
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D057286:Electronic Health Records; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D010641:Phenotype; D012307:Risk Factors; D014481:United States; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D055815:Young Adult
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D