title: Heritability of thyroid peroxidase autoantibody levels in type 1 diabetes: evidence from discordant twin pairs.
abstract: OBJECTIVE
  The discordance status of (autoimmune) type 1 diabetes within monozygotic twin pairs points to the importance of environmental factors. The aim of this study was to investigate whether the environmental events causing type 1 diabetes influence thyroid autoimmunity.
  
  
  METHODS
  Monozygotic and dizygotic twins discordant for type 1 diabetes from the UK and USA were tested for thyroid peroxidase autoantibodies (TPOA) by radioimmunoassay. Using quantitative genetic model fitting of a liability-threshold model we estimated the contribution of genetic (heritability) and environmental factors to TPOA.
  
  
  RESULTS
  TPOA positivity was higher in females than in males in both cohorts and was associated with later age at diagnosis in the UK and combined cohorts (p < 0.01). TPOA did not specifically segregate with type 1 diabetes in the twin pairs (p > 0.2 in all groups). The best-fitting models showed heritability (95% CI) estimates for TPOA of 63% (37%, 80%) for the UK and 80% (51%, 92%) for US twins, while the best-fitting meta-analysis model of the two twin cohorts combined included additive genetic and unique environmental factors with a heritability estimate of 69% (50%, 82%).
  
  
  CONCLUSIONS
  Risk of thyroid autoimmunity, defined by TPOA, in the context of autoimmune diabetes is, substantially, genetically determined in discordant twin pairs. Environmental factors leading to type 1 diabetes were not the same as those involved with thyroid autoimmunity. It follows that it is as important to investigate for thyroid autoimmunity in relatives of type 1 diabetes patients as it is in the patients themselves.
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center, Groningen, the Netherlands.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: Hawa
authors.forename: Frühling V
authors.initials: FV
authors.lastname: Rijsdijk
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Fain
authors.forename: Stavroula A
authors.initials: SA
authors.lastname: Paschou
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Steck
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
authors.forename: R David G
authors.initials: RD
authors.lastname: Leslie
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D004777:Environment; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007453:Iodide Peroxidase / Q000097:blood* / Q000276:immunology; D033862:Iron-Binding Proteins / Q000097:blood* / Q000276:immunology; D008297:Male; D011863:Radioimmunoassay; D013961:Thyroid Gland / Q000276:immunology; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D006113:United Kingdom; D014481:United States
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D033862:Iron-Binding Proteins; C056658:TPO protein, human; D007453:Iodide Peroxidase