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Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins
Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Celiac Disease Center, Columbia University Medical Center, Columbia University, New York, USA.
Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0003-0122-7234
Department of Genetics, University Medical Center, University of Groningen, Groningen, The Netherlands.
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2016 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 65, no 11, p. 1793-1798Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
London, United Kingdom: BMJ Publishing Group Ltd, 2016. Vol. 65, no 11, p. 1793-1798
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-50382DOI: 10.1136/gutjnl-2016-311713ISI: 000386471000006PubMedID: 27207974Scopus ID: 2-s2.0-84970002477OAI: oai:DiVA.org:oru-50382DiVA, id: diva2:931605
Funder
Swedish Society of MedicineSwedish Research CouncilAvailable from: 2016-05-30 Created: 2016-05-24 Last updated: 2018-07-13Bibliographically approved

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Halfvarson, JonasLudvigsson, Jonas F.

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