title: The relative importance of genetic and environmental factors in the aetiology of thyroid nodularity: a study of healthy Danish twins.
abstract: BACKGROUND
  A large proportion of healthy, euthyroid, nongoitrous individuals have thyroid nodules. The aetiology of these ultrasonographically detected morphological abnormalities is largely unknown. Factors such as age, gender, iodine intake, smoking and parity are associated with nodularity of the thyroid. Whether there is a genetic susceptibility is unclear.
  
  
  OBJECTIVE
  To gain insight into the aetiology of thyroid nodularity by investigating a large cohort of healthy euthyroid monozygotic and dizygotic twins.
  
  
  METHODS
  A cross-sectional twin study.
  
  
  METHODS
  A representative sample of self-reported healthy twin pairs was identified through the Danish Twin Registry. A total of 520 individuals divided into 104 monozygotic (MZ), 107 dizygotic same sex (DZ) and 49 opposite sex (OS) twin pairs were investigated.
  
  
  METHODS
  Probandwise concordance and tetrachoric correlations. Quantitative genetic modelling was used to elucidate the relative importance of genetic and environmental effects for the variation in the liability of nodularity.
  
  
  RESULTS
  A higher concordance rate for thyroid nodularity was found in MZ twins [0.57 (95% CI 0.36-0.76)] than in DZ twins [0.36 (95% CI 0.17-0.56, P = 0.074)]. The same was true for tetrachoric correlations: 0.67 (95% CI 0.34-0.87) in MZ twins and 0.17 (CI - 0.28-0.56, P = 0.053) in DZ twins. The difference, although not significant, was more pronounced for multiple nodules than for solitary nodules. Controlling for covariates (age, gender and smoking habits), it was calculated that genetic factors accounted for 67% (95% CI 35-87%) and environmental factors for 33% (95% CI 13-65%) of the individual differences in the liability to thyroid nodularity.
  
  
  CONCLUSIONS
  This study suggests that genetic factors are of aetiological importance for thyroid nodularity in clinically healthy and euthyroid individuals, and indicates a difference in the aetiology of solitary and multiple thyroid nodules.
authors.affiliation: Department of Endocrinology M, Odense University Hospital, Odense C, Denmark. piaskovhansen@dadlnet.dk
authors.forename: Pia Skov
authors.initials: PS
authors.lastname: Hansen
authors.forename: Thomas Heiberg
authors.initials: TH
authors.lastname: Brix
authors.forename: Finn Noe
authors.initials: FN
authors.lastname: Bennedbaek
authors.forename: Steen Joop
authors.initials: SJ
authors.lastname: Bonnema
authors.forename: Ivan
authors.initials: I
authors.lastname: Iachine
authors.forename: Kirsten Ohm
authors.initials: KO
authors.lastname: Kyvik
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hegedüs
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D004200:Diseases in Twins / Q000209:etiology / Q000235:genetics*; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries; D012044:Regression Analysis; D012307:Risk Factors; D016606:Thyroid Nodule / Q000209:etiology / Q000235:genetics*; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic