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Genome screening of coeliac disease
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  1. S Popat1,
  2. S Bevan1,
  3. C P Braegger2,
  4. A Busch3,
  5. D O'Donoghue4,
  6. K Falth-Magnusson5,
  7. A Godkin6,
  8. L Hogberg7,
  9. G Holmes8,
  10. K B Hosie9,
  11. P D Howdle10,
  12. H Jenkins1,
  13. D Jewell6,
  14. S Johnston11,
  15. N P Kennedy12,
  16. P Kumar13,
  17. R F A Logan14,
  18. A H G Love11,
  19. M N Marsh16,
  20. C J Mulder17,
  21. K Sjoberg18,
  22. L Stenhammar7,
  23. J Walker-Smith19,
  24. R S Houlston1
  1. 1Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK
  2. 2University Children's Hospital, Steinwiesstrass 75, Zurich, Switzerland
  3. 3Kinderpoliklinik, Eberhard-Karls-Universitat, Tubingen, Germany
  4. 4Gastroenterology and Liver Unit, St Vincent's Hospital, Dublin, Ireland
  5. 5Department of Paediatrics, Linkoping University, Sweden
  6. 6Gastroenterology Unit, The Radcliffe Infirmary, Oxford, UK
  7. 7Department of Paediatrics, Norrkoping Hospital, Sweden
  8. 8Department of Medicine, Derbyshire Royal Infirmary, Derby, UK
  9. 9University Surgical Unit, Northern General Hospital, Sheffield, UK
  10. 10Division of Medicine, St James's University Hospital, Leeds, UK
  11. 11Department of Child Health, University Hospital of Wales, Cardiff, UK
  12. 12Department of Gastroenterology, Belfast City Hospital Trust, Belfast, UK
  13. 13Department of Clinical Medicine, Trinity Centre, St James' Hospital, Dublin, Ireland
  14. 14Department of Gastroenterology, St Bartholomew's Hospital, London, UK
  15. 15Department of Public Health and Epidemiology, University Hospital, Nottingham, UK
  16. 16University Department of Medicine, Hope Hospital, Salford, Manchester, UK
  17. 17Hepatogastroenterology, Rijnstate Hospital, Arnhem, The Netherlands
  18. 18Department of Medicine, University of Lund, Malmo, Sweden
  19. 19University Department of Paediatric Gastroenterology, Royal Free Hospital, London, UK
  1. Correspondence to:
 Dr S Popat, Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK;
 s.popat{at}icr.ac.uk

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Coeliac disease is caused by T cell sensitisation of the intestine to cereal prolamins, which results in a range of mucosal abnormalities that may lead to malabsorption.1 The population prevalence in western countries is ∼1 in 200.2–4 Evidence for an inherited predisposition to coeliac disease comes from studies of first degree relatives of patients and studies of twins.5,6 A strong association is seen between coeliac disease and the HLA-DQ (α1*05, β1*02) heterodimer (DQ2) which is present in approximately 95% of patients,7–9 compared with 20-30% of healthy subjects.10,11 The difference in concordance rates between monozygotic twins and HLA identical sibs (80-100% v 25%) implicates non-HLA genes in the genetic predisposition to coeliac disease.11 The overall relative risk in sibs is at least 20 and is therefore four-fold higher than that attributable to HLA alone under model of inheritance.7 Genome linkage searches carried out on Irish,12 Italian,13, and UK14 coeliac disease families have identified a number of potential sites for the location of non-HLA linked genes. The putative candidate loci detected in the three studies are, however, largely inconsistent and the findings have not been replicated in other populations.15–19 Here we report the results of a genome screen of 24 multiplex families with coeliac disease and discuss the findings of this study in relation to previously published analyses.

METHODS AND RESULTS

Twenty-four families with two or more members affected with coeliac disease were recruited for this study (fig 1). Nine of these families (Nos 1, 3, 4, 6, 30, 32, 39, 43, and 44) have been used in a previous study of candidate regions.16 All the families were of northern European ancestry. Twelve of the families were recruited from the UK, nine from Sweden, two from Switzerland, …

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