title: Circulating testosterone and SHBG concentrations are heritable in women: the Framingham Heart Study.
abstract: BACKGROUND
  Many factors influence the concentration of circulating testosterone and its primary binding protein, SHBG. However, little is known about the genetic contribution to their circulating concentrations in women, and their heritability in women is not well established.
  
  
  OBJECTIVE
  Our objective was to estimate the heritability of circulating total testosterone (TT), free testosterone (FT), and SHBG in women in families from the Framingham Heart Study.
  
  
  METHODS
  Women in the Framingham Heart Study who were not pregnant, had not undergone bilateral oophorectomy, and were not using exogenous hormones were eligible for this investigation. TT was measured using liquid chromatography tandem mass spectrometry and SHBG using an immunofluorometric assay (Delfia-Wallac), and FT was calculated. Heritability estimates were calculated using variance-components methods in Sequential Oligogenic Linkage Analysis Routines (SOLAR) and were adjusted for age, age(2), body mass index (BMI), BMI(2), diabetes, smoking, and menopausal status. Bivariate analyses were done to assess genetic correlation between TT, FT, and SHBG.
  
  
  RESULTS
  A total of 2685 women were studied including 868 sister pairs and 688 mother-daughter pairs. Multivariable adjusted heritability estimates were 0.26 ± 0.05 for FT, 0.26 ± 0.05 for TT, and 0.56 ± 0.05 for SHBG (P < 1.0 × 10(-7) for all). TT was genetically correlated with SHBG [genetic correlation coefficient (ρG) = 0.31 ± 0.10] and FT (ρG = 0.54 ± 0.09), whereas SHBG was inversely correlated with FT (ρG = -0.60 ± 0.08).
  
  
  CONCLUSIONS
  Circulating TT, FT, and SHBG concentrations in women are significantly heritable, underscoring the importance of further work to identify the specific genes that contribute significantly to variation in sex steroid concentrations in women. The strong shared genetic component among pairs of TT, FT, and SHBG concentrations suggests potential pleiotropic effects for some of the underlying genes.
authors.affiliation: Sections of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston University School of Public Health, Boston, Massachusetts 02118, USA. coviello@bu.edu
authors.forename: A D
authors.initials: AD
authors.lastname: Coviello
authors.forename: W V
authors.initials: WV
authors.lastname: Zhuang
authors.forename: K L
authors.initials: KL
authors.lastname: Lunetta
authors.forename: S
authors.initials: S
authors.lastname: Bhasin
authors.forename: J
authors.initials: J
authors.lastname: Ulloor
authors.forename: A
authors.initials: A
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Karasik
authors.forename: D P
authors.initials: DP
authors.lastname: Kiel
authors.forename: R S
authors.initials: RS
authors.lastname: Vasan
authors.forename: J M
authors.initials: JM
authors.lastname: Murabito
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000235:genetics* / Q000378:metabolism; D013739:Testosterone / Q000097:blood / Q000235:genetics*
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone