title: Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ralf
authors.identifier: 0000-0002-3765-2067
authors.initials: R
authors.lastname: Kuja-Halkola
authors.affiliation: Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Medicine, Celiac Disease Center, Columbia University Medical Center, Columbia University, New York, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lebwohl
authors.affiliation: Faculty of Medicine and Health, Department of Gastroenterology, Örebro University, Örebro, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Halfvarson
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center, Groningen, The Netherlands.
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.affiliation: Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
authors.affiliation: Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.|Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, City Hospital, Nottingham, UK.
authors.forename: Jonas F
authors.initials: JF
authors.lastname: Ludvigsson
mesh_terms: D001706:Biopsy / Q000379:methods; D002446:Celiac Disease / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004777:Environment; D005260:Female; D014644:Genetic Variation / Q000502:physiology; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D007421:Intestine, Small / Q000473:pathology*; D008297:Male; D020412:Multifactorial Inheritance / Q000502:physiology*; D015995:Prevalence; D012042:Registries; D013548:Sweden / Q000453:epidemiology; D014429:Twins, Dizygotic / Q000235:genetics / Q000706:statistics & numerical data; D014430:Twins, Monozygotic / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: D006683:HLA-DQ Antigens
keywords: AUTOIMMUNE DISEASE; GLUTEN