Circulating testosterone and SHBG concentrations are heritable in women

The Framingham Heart Study

Andrea D. Coviello, W. V. Zhuang, K. L. Lunetta, S. Bhasin, J. Ulloor, A. Zhang, D. Karasik, D. P. Kiel, R. S. Vasan, J. M. Murabito

Research output: Contribution to journalArticle

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Abstract

Context: 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). Conclusion: 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.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number9
DOIs
StatePublished - Sep 2011
Externally publishedYes

Fingerprint

Testosterone
Body Mass Index
Genes
Fluoroimmunoassay
Liquid chromatography
Ovariectomy
Medical problems
Tandem Mass Spectrometry
Nuclear Family
Liquid Chromatography
Mass spectrometry
Siblings
Assays
Carrier Proteins
Smoking
Steroids
Mothers
Hormones

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Coviello, A. D., Zhuang, W. V., Lunetta, K. L., Bhasin, S., Ulloor, J., Zhang, A., ... Murabito, J. M. (2011). Circulating testosterone and SHBG concentrations are heritable in women: The Framingham Heart Study. Journal of Clinical Endocrinology and Metabolism, 96(9). https://doi.org/10.1210/jc.2011-0050

Circulating testosterone and SHBG concentrations are heritable in women : The Framingham Heart Study. / Coviello, Andrea D.; Zhuang, W. V.; Lunetta, K. L.; Bhasin, S.; Ulloor, J.; Zhang, A.; Karasik, D.; Kiel, D. P.; Vasan, R. S.; Murabito, J. M.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 9, 09.2011.

Research output: Contribution to journalArticle

Coviello, AD, Zhuang, WV, Lunetta, KL, Bhasin, S, Ulloor, J, Zhang, A, Karasik, D, Kiel, DP, Vasan, RS & Murabito, JM 2011, 'Circulating testosterone and SHBG concentrations are heritable in women: The Framingham Heart Study', Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 9. https://doi.org/10.1210/jc.2011-0050
Coviello, Andrea D. ; Zhuang, W. V. ; Lunetta, K. L. ; Bhasin, S. ; Ulloor, J. ; Zhang, A. ; Karasik, D. ; Kiel, D. P. ; Vasan, R. S. ; Murabito, J. M. / Circulating testosterone and SHBG concentrations are heritable in women : The Framingham Heart Study. In: Journal of Clinical Endocrinology and Metabolism. 2011 ; Vol. 96, No. 9.
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abstract = "Context: 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). Conclusion: 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.",
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AU - Lunetta, K. L.

AU - Bhasin, S.

AU - Ulloor, J.

AU - Zhang, A.

AU - Karasik, D.

AU - Kiel, D. P.

AU - Vasan, R. S.

AU - Murabito, J. M.

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N2 - Context: 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). Conclusion: 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.

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