title: A genomewide screen in a four-generation Dutch family with celiac disease: evidence for linkage to chromosomes 6 and 9.
abstract: OBJECTIVE
  Celiac disease is caused by the interaction of multiple genes and environmental factors. Inheritance of the disease shows a complex pattern with a 10% sibling recurrence risk. The HLA-region is a major genetic risk locus in celiac disease, but genes outside this region are expected to contribute to the disease risk as well. The aim of this study was to identify the loci causing celiac disease in one large Dutch family with apparent dominant transmission of the disease.
  
  
  METHODS
  The family comprised 17 patients in four generations, with possible transmission of the disease by both grandparents. Microsatellite markers evenly spread over all chromosomes were genotyped and linkage analysis was performed using both dominant and recessive disease models and a model-free analysis.
  
  
  RESULTS
  Disease susceptibility in the family was linked to the HLA-region (lod score of 2.33) and all patients were HLA-DQ2. A dominantly inherited non-HLA locus with a maximum lod score of 2.61 was detected at 9p21-13, which was shared by 16 patients. Model-free analysis identified another possible non-HLA locus, at 6q25.3, which was shared by 14 patients (p = 0.01). Neither of these regions was detected in a genomewide screen in Dutch affected sibpairs, but the 9p21 locus has been implicated in Scandinavian families.
  
  
  CONCLUSIONS
  Two potential non-HLA loci for celiac disease were identified in this large Dutch family. Our results provide replication of the Scandinavian 9p21 locus, and suggest that this locus plays a role in celiac disease patients from different Caucasian populations.
authors.affiliation: Department of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Martine J
authors.initials: MJ
authors.lastname: van Belzen
authors.forename: Martine M
authors.initials: MM
authors.lastname: Vrolijk
authors.forename: Jos W R
authors.initials: JW
authors.lastname: Meijer
authors.forename: J Bart A
authors.initials: JB
authors.lastname: Crusius
authors.forename: Peter L
authors.initials: PL
authors.lastname: Pearson
authors.forename: Lodewijk A
authors.initials: LA
authors.lastname: Sandkuijl
authors.forename: Roderick H J
authors.initials: RH
authors.lastname: Houwen
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002446:Celiac Disease / Q000235:genetics*; D002648:Child; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010375:Pedigree