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Original article
Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins
  1. Ralf Kuja-Halkola1,
  2. Benjamin Lebwohl1,2,
  3. Jonas Halfvarson3,
  4. Cisca Wijmenga4,
  5. Patrik K E Magnusson1,
  6. Jonas F Ludvigsson1,5,6
  1. 1Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  2. 2Department of Medicine, Celiac Disease Center, Columbia University Medical Center, Columbia University, New York, USA
  3. 3Faculty of Medicine and Health, Department of Gastroenterology, Örebro University, Örebro, Sweden
  4. 4Department of Genetics, University of Groningen, University Medical Center, Groningen, The Netherlands
  5. 5Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
  6. 6Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, City Hospital, Nottingham, UK
  1. Correspondence to Dr Jonas F Ludvigsson, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden; jonasludvigsson{at}yahoo.com

Abstract

Background and objective Almost 100% individuals with coeliac disease (CD) are carriers of the human leucocyte antigen (HLA) DQ2/DQ8 alleles. Earlier studies have, however, failed to consider the HLA system when estimating heritability in CD, thus violating an underlying assumption of heritability analysis. We examined the heritability of CD in a large population-based sample of twins, considering HLA.

Design In a population-representative sample of 107 912 twins, we identified individuals with CD (equal to villous atrophy) through biopsy reports from all Swedish pathology departments. We calculated concordance rates and tetrachoric correlations for monozygotic (MZ) and dizygotic (DZ) twin pairs. Further, we estimated heritability of CD, first strictly from observed data, and then the non-HLA heritability, representing the heritability of all genetic factors except the HLA locus, using an approach that circumvent the violation of underlying assumptions.

Results We identified 513 twins with a diagnosis of CD (prevalence 0.48%). Concordance rates were higher in MZ pairs (0.49) than in DZ pairs (0.10), as were tetrachoric correlations (0.89 in MZ vs 0.51 in DZ pairs). The heritability of CD was 75% (95% CI 55% to 96%). The non-HLA heritability was slightly attenuated, 68% (95% CI 40% to 96%), with shared (17%) and non-shared (15%) environmental factors explaining the remaining variability of CD.

Conclusions CD is characterised by a high heritability, but our study also suggests that non-shared environmental factors may be of importance to CD development. HLA seems to have only moderate impact on heritability estimates.

  • AUTOIMMUNE DISEASE
  • GLUTEN

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Footnotes

  • Contributors ICMJE criteria for authorship read and met: JFL, RKH, BL, JH, CW and PKEM. Agreed with the manuscript's results and conclusions. Approved the final version of the manuscript: JFL, RKH, BL, JH, CW and PKEM. Designed the study: JFL, RKH and PKEM. Analysed the data: RKH. Wrote the first draft of the paper: JFL and RKH. Contributed to the writing of the paper: BL, JH, CW and PKEM. Contributed to the design of study and interpretation of the data analyses: BL, JH, CW. Responsible for data integrity: JFL, RKH and PKEM. Obtained funding: JFL.

  • Funding JFL was supported by grants from the Swedish Society of Medicine and the Swedish Research Council.

  • Competing interests None declared

  • Ethics approval This project (2006/633-31/4) was approved by the Regional Ethical Review Board in Stockholm (Karolinska Institutet), Sweden on 14 June 2006.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data can be obtained through the Swedish National Board of Statistics upon request.

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