Multiple independent variants in 6q21-22 associated with susceptibility to celiac disease in the Dutch, Finnish and Hungarian populations

Elisabet Einarsdottir*, Marianna R. Bevova, Alexandra Zhernakova, Alienke Monsuur, Lotta L. E. Koskinen, Ruben van't Slot, Chris Mulder, M. Luisa Mearin, Ilma R. Korponay-Szabo, Katri Kaukinen, Kalle Kurppa, Juha Kere, Markku Maki, Cisca Wijmenga, Paivi Saavalainen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

Celiac disease is an inflammatory enteropathy caused by intolerance to gluten. Previous linkage studies in the Dutch, Finnish and Hungarian populations have revealed a locus on chromosome 6q21-22 conferring susceptibility to celiac disease. This locus has previously been implicated in susceptibility to other autoimmune diseases such as Crohn's disease and type 1 diabetes. We performed fine mapping on 446 independent individuals with celiac disease and 641 controls of Dutch origin, testing 872 tagging SNPs in a 22Mb region of chromosome 6. The 12 most promising SNPs were followed up in 2071 individuals from 284 Finnish and 357 Hungarian celiac disease families to identify risk variants in this region. Multiple markers in the region were significantly associated with celiac disease in the Dutch material. Two SNPs, rs9391227 and rs4946111, were significantly associated with celiac disease in the Finnish population. The association to rs9391227 represents the strongest association signal found in the Finnish (P=0.003, OR 0.66) as well as the combined Dutch, Finnish and Hungarian populations (P=3.6x10(-5), OR 0.76). The rs9391227 is situated downstream of the HECT domain and ankyrin repeat containing, E3 ubiquitin protein ligase 1 (HACE1) gene and is contained within a region of strong linkage disequilibrium enclosing HACE1. Two additional, independent, susceptibility variants in the 6q21-22 region were also found in a meta-analysis of the three populations. The 6q21-22 region was confirmed as a celiac disease susceptibility locus and harbors multiple independent associations, some of which may implicate ubiquitin-pathways in celiac disease susceptibility. European Journal of Human Genetics (2011) 19, 682-686; doi:10.1038/ejhg.2011.2; published online 16 February 2011

Original languageEnglish
Pages (from-to)682-686
Number of pages5
JournalEuropean Journal of Human Genetics
Volume19
Issue number6
DOIs
Publication statusPublished - Jun-2011

Keywords

  • Celiac
  • linkage
  • association
  • genome-wide
  • 6q21-22
  • RISK VARIANTS
  • LINKAGE
  • GENE
  • DYSPLASIA
  • COMPLEX
  • GLUTEN
  • REGION
  • LOCUS
  • MAPS

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