title: Genome-wide association analysis in sarcoidosis and Crohn's disease unravels a common susceptibility locus on 10p12.2.
abstract: OBJECTIVE
  Crohn's disease (CD) and sarcoidosis (SA) are chronic inflammatory barrier diseases that share several clinical and immunological features, including the occurrence of granulomas.
  
  
  METHODS
  A 100k genome-wide association study with 83,360 single-nucleotide polymorphisms (SNPs) was performed on 382 CD patients, 398 SA patients, and 394 control individuals. The 24 SNPs that were most strongly associated in the combined CD/SA phenotype were selected for verification in an independent sample of 1,317 patients (660 CD and 657 SA) and 1,091 controls.
  
  
  RESULTS
  The most significant association (Bonferroni corrected P = .036) was obtained at SNP rs1398024 on chromosome 10p12.2, with an odds ratio (OR) for both diseases of 0.81 (95% confidence interval [CI], 0.69-0.96) for carriership of the rarer allele A. The P value in the overall combined sample was 4.24 x 10(-6). During further follow-up, a moderate association (OR, 0.83; 95% CI, 0.72-0.96; P = .015) was observed between rs1398024 and ulcerative colitis (1,080 patients vs 1,091 controls), the second main subphenotype of inflammatory bowel disease in addition to CD. Extensive fine mapping of the 10p12.2 locus points to yet unidentified variants in the C10ORF67 gene region as the most likely underlying risk factors.
  
  
  CONCLUSIONS
  Our study demonstrates that the combined analysis of different, albeit clinically related, phenotypes can lead to the identification of common susceptibility loci.
authors: Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
authors: Andre
authors: A
authors: Franke
authors: Annegret
authors: A
authors: Fischer
authors: Michael
authors: M
authors: Nothnagel
authors: Christian
authors: C
authors: Becker
authors: Nils
authors: N
authors: Grabe
authors: Andreas
authors: A
authors: Till
authors: Tim
authors: T
authors: Lu
authors: Joachim
authors: J
authors: Müller-Quernheim
authors: Michael
authors: M
authors: Wittig
authors: Alexander
authors: A
authors: Hermann
authors: Tobias
authors: T
authors: Balschun
authors: Sylvia
authors: S
authors: Hofmann
authors: Regina
authors: R
authors: Niemiec
authors: Sabrina
authors: S
authors: Schulz
authors: Jochen
authors: J
authors: Hampe
authors: Susanna
authors: S
authors: Nikolaus
authors: Peter
authors: P
authors: Nürnberg
authors: Michael
authors: M
authors: Krawczak
authors: Manfred
authors: M
authors: Schürmann
authors: Philip
authors: P
authors: Rosenstiel
authors: Almut
authors: A
authors: Nebel
authors: Stefan
authors: S
authors: Schreiber
mesh_terms: D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D015894:Genome, Human; D023281:Genomics; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012507:Sarcoidosis / Q000453:epidemiology / Q000235:genetics*