title: Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort.
abstract: OBJECTIVE
  Thyroid hormone action influences many metabolic and synthetic processes, but the degree of regulation attributed to genes and environmental factors affecting normal variation remains controversial.
  
  
  METHODS
  We investigated the magnitude of the genetic and environmental determination of serum concentrations of free (f) T3, fT4, TSH and the fT4 x TSH product and their variation, in a large cohort of twin pairs. Female dizygous and monozygous twins (849 and 213 pairs, respectively) from the TwinsUK registry (mean age 45.5, range 18-80 years) were studied.
  
  
  RESULTS
  Comparison of thyroid parameters within various groups showed no differences between smoking categories, and higher serum TSH and lower fT3 in subjects with positive thyroid antibodies. Using structural equation modelling, we estimated the heritable contribution to serum thyroid parameters (with 95% confidence intervals) to be 65% (58%-71%) for TSH, 65% (58%-71%) for the fT4 x TSH product, 39% (20%-55%) for fT4 and 23% (3%-41%) for fT3.
  
  
  CONCLUSIONS
  We conclude that genetic regulation is a particularly important determinant of TSH and the fT4 x TSH product, and is a less important determinant of fT4 and fT3 concentrations in Caucasian women. These data from a large well-characterized cohort suggest that while there is a strong heritable contribution to serum TSH, variation in fT4 and fT3 concentrations may be less explained by genetic factors and more driven by environmental effects than previously thought.
authors.affiliation: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Panicker
authors.forename: S G
authors.initials: SG
authors.lastname: Wilson
authors.forename: T D
authors.initials: TD
authors.lastname: Spector
authors.forename: S J
authors.initials: SJ
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Falchi
authors.forename: J B
authors.initials: JB
authors.lastname: Richards
authors.forename: G L
authors.initials: GL
authors.lastname: Surdulescu
authors.forename: E M
authors.initials: EM
authors.lastname: Lim
authors.forename: S J
authors.initials: SJ
authors.lastname: Fletcher
authors.forename: J P
authors.initials: JP
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000502:physiology*; D013961:Thyroid Gland / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood* / Q000235:genetics; D013974:Thyroxine / Q000097:blood* / Q000235:genetics; D014284:Triiodothyronine / Q000097:blood* / Q000235:genetics; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics; D006113:United Kingdom
chemical_list: D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine