title: Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship.
abstract: OBJECTIVE
  Identifying shared and disease-specific susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC) would help define the biologic relationship between the inflammatory bowel diseases. More than 30 CD susceptibility loci have been identified. These represent important candidate susceptibility loci for UC. Loci discovered by the index genome scans in CD have previously been tested for association with UC, but those identified in the recent meta-analysis await such investigation. Furthermore, the recently identified UC locus at ECM1 requires formal testing for association with CD.
  
  
  METHODS
  We analyzed 45 single nucleotide polymorphisms, tagging 29 of the loci recently associated with CD in 2527 UC cases and 4070 population controls. We also genotyped the UC-associated ECM1 variant rs11205387 in 1560 CD patients and 3028 controls.
  
  
  RESULTS
  Nine regions showed association with UC at a threshold corrected for the 29 loci tested (P < .0017). The strongest association (P = 4.13 x 10(-8); odds ratio = 1.27) was identified with a 170-kilobase region on chromosome 1q32 that contains 3 genes. We also found association with JAK2 and replicated a recently reported association with STAT3, further implicating the role of this signaling pathway in inflammatory bowel disease. Additional novel UC susceptibility genes were LYRM4 and CDKAL1. Twenty of the loci were not associated with UC, and several appear to be specific to CD. ECM1 variation was not associated with CD.
  
  
  CONCLUSIONS
  Collectively, these data help define the genetic relationship between CD and UC and characterize common, as well as disease-specific mechanisms of pathogenesis.
authors.affiliation: Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Anderson
authors.forename: Dunecan C O
authors.initials: DC
authors.lastname: Massey
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Barrett
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Prescott
authors.forename: Mark
authors.initials: M
authors.lastname: Tremelling
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Fisher
authors.forename: Rhian
authors.initials: R
authors.lastname: Gwilliam
authors.forename: Jemima
authors.initials: J
authors.lastname: Jacob
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Nimmo
authors.forename: Hazel
authors.initials: H
authors.lastname: Drummond
authors.forename: Charlie W
authors.initials: CW
authors.lastname: Lees
authors.forename: Clive M
authors.initials: CM
authors.lastname: Onnie
authors.forename: Catherine
authors.initials: C
authors.lastname: Hanson
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Blaszczyk
authors.forename: Radhi
authors.initials: R
authors.lastname: Ravindrarajah
authors.forename: Sarah
authors.initials: S
authors.lastname: Hunt
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Varma
authors.forename: Naomi
authors.initials: N
authors.lastname: Hammond
authors.forename: Gregory
authors.initials: G
authors.lastname: Lewis
authors.forename: Heather
authors.initials: H
authors.lastname: Attlesey
authors.forename: Nick
authors.initials: N
authors.lastname: Watkins
authors.forename: Willem
authors.initials: W
authors.lastname: Ouwehand
authors.forename: David
authors.initials: D
authors.lastname: Strachan
authors.forename: Wendy
authors.initials: W
authors.lastname: McArdle
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
authors.forename: Alan
authors.initials: A
authors.lastname: Lobo
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sanderson
authors.forename: Derek P
authors.initials: DP
authors.lastname: Jewell
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: John C
authors.initials: JC
authors.lastname: Mansfield
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Mathew
authors.forename: Jack
authors.initials: J
authors.lastname: Satsangi
authors.forename: Miles
authors.initials: M
authors.lastname: Parkes
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000235:genetics; D012359:tRNA Methyltransferases
chemical_list: C490607:ECM1 protein, human; D016326:Extracellular Matrix Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D012359:tRNA Methyltransferases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human