Abstract
Celiac disease (CD) is a common chronic inflammatory disorder of the small intestine with a multifactorial aetiology. HLA is a well-known risk factor, but other genetic factors also influence disease susceptibility. To identify the genes involved in this disorder, we performed a genome-wide scan on 106 well-defined Swedish and Norwegian families with at least two affected siblings. We investigated familial segregation of 398 microsatellite markers, and utilised non-parametric linkage analysis. The strongest linkage with disease was found to the HLA locus (6p) (P<0.000006). There were eight regions besides HLA with a point wise P value below 0.05. Among these eight regions were 11q and 5q, both of which have been suggested in several linkage studies of independent celiac disease families. We also performed a stratification analysis of families according to their HLA genotypes. This resulted in significant differences on chromosome 2q. These results indicate that 11q, 5q and possibly also 2q are true susceptibility regions in CD.
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Acknowledgements
We would like to thank Britt-Marie Käck and The Celiac Society in Sweden for help in collecting families and blood samples, Bente Talseth for HLA typing, and all the families participating in the study. The work was supported by grants from the Foundation for Strategic Research, the Swedish Medical Research Council (Project no. K98-13X-12568-01A and K2000-27X-12568-03A), the Gothenburg Medical Society, the European Commission (QLRT-1999-00037), EXTRA funds from the Norwegian Foundation for Health and Rehabilitation, Aktieselskabet Freia Chocolade Fabriks Medicinske Fond, The Swedish Society of Medicine, Frimurare-Barnhusdirektionen, The Foundation of the National Board of Health and Welfare, Sigurd and Elsa Goljes Memory Foundation and the Wilhelm and Martina Lundgren Research Foundation.
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Naluai, Å., Nilsson, S., Gudjónsdóttir, A. et al. Genome-wide linkage analysis of Scandinavian affected sib-pairs supports presence of susceptibility loci for celiac disease on chromosomes 5 and 11. Eur J Hum Genet 9, 938–944 (2001). https://doi.org/10.1038/sj.ejhg.5200752
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DOI: https://doi.org/10.1038/sj.ejhg.5200752
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