title: A genome-wide linkage analysis in 181 German sarcoidosis families using clustered biallelic markers.
abstract: BACKGROUND
  Sarcoidosis (SA) is a systemic granulomatous inflammatory disorder with complex etiology and strong clustering in families. Genome-wide association studies have been successful in the identification of common risk variants for the disease. To reveal susceptibility variants with low frequencies but strong effects, we performed a genome-wide linkage scan in a large sample of SA families.
  
  
  METHODS
  We genotyped 528 members of 181 German SA families for 3,882 single nucleotide polymorphism assays from the SNPlex System Human Linkage Mapping Set 4K.
  
  
  RESULTS
  Nonparametric linkage analysis revealed one region of suggestive linkage on chromosome 12p13.31 at 20 cM (logarithm of odds [LOD] = 2.53; local P value = .0003) and another linkage peak of nearly suggestive linkage on 9q33.1 at 134 cM (LOD = 2.12; local P value = .0009). The latter has been reported to show suggestive evidence for linkage in a sample of 229 African American SA families previously. Analysis of acute and chronically affected families revealed a subphenotype-specific linkage pattern and an additional, nearly suggestive linkage peak on chromosome 16p13.11 at 38 cM (LOD = 2.09; local P value = .001), which was confined to acute SA.
  
  
  CONCLUSIONS
  Our results propose that the respective regions might harbor yet-unidentified, possibly subphenotype-specific risk factors for the disease (eg, with immune-related functions like the tumor necrosis factor receptor 1). They should be proved to be important for SA pathogenesis and investigated in detail with an emphasis on rare variants. Subphenotype-specific risk factors might serve for prognosis of the clinical course of the disease.
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Fischer
authors.forename: Michael
authors.initials: M
authors.lastname: Nothnagel
authors.forename: Manfred
authors.initials: M
authors.lastname: Schürmann
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller-Quernheim
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hofmann
mesh_terms: D000483:Alleles; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012507:Sarcoidosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism
chemical_list: D005819:Genetic Markers