title: A novel sarcoidosis risk locus for Europeans on chromosome 11q13.1.
abstract: BACKGROUND
  Sarcoidosis is a complex inflammatory disease with a heterogeneous clinical picture. Among others, an acute and chronic clinical course can be distinguished, for which specific genetic risk factors are known.
  
  
  OBJECTIVE
  To identify additional risk loci for sarcoidosis and its acute and chronic subforms, we analyzed imputed data from a genome-wide association scan for these phenotypes.
  
  
  METHODS
  After quality control, the genome-wide association scan comprised nearly 1.3 million imputed single-nucleotide polymorphisms based on an Affymetrix 6.0 Gene Chip dataset of 564 German sarcoidosis cases, including 176 acute and 354 chronic cases and 1,575 control subjects.
  
  
  RESULTS
  We identified chromosome 11q13.1 (rs479777) as a novel locus influencing susceptibility to sarcoidosis with genome-wide significance. The marker was significantly associated in three distinct German case-control populations and in an additional German family sample with odds ratios ranging from 0.67 to 0.77. This finding was further replicated in two independent European case-control populations from the Czech Republic (odds ratio, 0.75) and from Sweden (odds ratio, 0.79). In a meta-analysis of the included European case-control samples the marker yielded a P value of 2.68 × 10(-18). The locus was previously reported to be associated with Crohn disease, psoriasis, alopecia areata, and leprosy. For sarcoidosis, fine-mapping and expression analysis suggest KCNK4, PRDX5, PCLB3, and most promising CCDC88B as candidates for the underlying risk gene in the associated region.
  
  
  CONCLUSIONS
  This study provides striking evidence for association of chromosome 11q13.1 with sarcoidosis in Europeans, and thus identified a further genetic risk locus shared by sarcoidosis, Crohn disease and psoriasis.
authors: Christian-Albrechts University, Institute of Clinical Molecular Biology, Schittenhelmstrasse 12, Kiel, Germany. s.schreiber@mucosa.de
authors: Annegret
authors: A
authors: Fischer
authors: Benjamin
authors: B
authors: Schmid
authors: David
authors: D
authors: Ellinghaus
authors: Michael
authors: M
authors: Nothnagel
authors: Karoline I
authors: KI
authors: Gaede
authors: Manfred
authors: M
authors: Schürmann
authors: Simone
authors: S
authors: Lipinski
authors: Philip
authors: P
authors: Rosenstiel
authors: Gernot
authors: G
authors: Zissel
authors: Kerstin
authors: K
authors: Höhne
authors: Martin
authors: M
authors: Petrek
authors: Vitezslav
authors: V
authors: Kolek
authors: Stefan
authors: S
authors: Pabst
authors: Christian
authors: C
authors: Grohé
authors: Johan
authors: J
authors: Grunewald
authors: Marcus
authors: M
authors: Ronninger
authors: Anders
authors: A
authors: Eklund
authors: Leonid
authors: L
authors: Padyukov
authors: Christian
authors: C
authors: Gieger
authors: H-Erich
authors: HE
authors: Wichmann
authors: Almut
authors: A
authors: Nebel
authors: Andre
authors: A
authors: Franke
authors: Joachim
authors: J
authors: Müller-Quernheim
authors: Sylvia
authors: S
authors: Hofmann
authors: Stefan
authors: S
authors: Schreiber
mesh_terms: D000208:Acute Disease; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002908:Chronic Disease; D003424:Crohn Disease / Q000235:genetics*; D018153:Czech Republic; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005858:Germany; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012507:Sarcoidosis / Q000235:genetics*; D013548:Sweden
chemical_list: C559603:CCDC88B protein, human; D002352:Carrier Proteins