The heritability of circulating testosterone, oestradiol, oestrone and sex hormone binding globulin concentrations in men: The Framingham Heart Study

T. G. Travison, W. V. Zhuang, K. L. Lunetta, D. Karasik, S. Bhasin, D. P. Kiel, A. D. Coviello, J. M. Murabito

    Research output: Contribution to journalArticle

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    Abstract

    Objective Circulating testosterone, oestradiol and oestrone concentrations vary considerably between men. Although a substantial proportion of this variation may be attributed to morbidity and behavioural factors, these cannot account for its entirety, suggesting genetic inheritance as a potential additional determinant. The analysis described here was intended to estimate the heritability of male circulating total testosterone (TT), calculated free testosterone (cFT), oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG), along with the genetic correlation between these factors. Design Cross-sectional, observational analysis of data from male members of the Offspring and Generation 3 cohorts of the Framingham Heart Study. Data were collected in the years 1998-2005. Participants A total of 3367 community-dwelling men contributed to the analysis, including 1066 father/son and 1284 brother pairs among other family relationships. Measurements Levels of serum sex steroids (TT, E1 and E2) were measured by liquid chromatography-tandem mass spectrometry, SHBG by immunofluorometric assay and cFT by mass action equation. Heritability was obtained using variance components analysis with adjustment for covariates including age, diabetes mellitus, body mass index and smoking status. Results Age-adjusted heritability estimates were 0·19, 0·40, 0·40, 0·30 and 0·41 for cFT, TT, E1, E2 and SHBG, respectively. Adjustment for covariates did not substantially attenuate these estimates; SHBG-adjusted TT results were similar to those obtained for cFT. Genetic correlation coefficients (ρG) indicated substantial genetic association between TT and cFT (ρG = 0·68), between TT and SHBG (pG = 0·87), between E1 and E2 (ρG = 0·46) and between TT and E2 (ρG = 0·48). Conclusion Circulating testosterone, oestradiol and oestrone concentrations exhibit substantial heritability in adult men. Significant genetic association between testosterone and oestrogen levels suggests shared genetic pathways.

    Original languageEnglish
    Pages (from-to)277-282
    Number of pages6
    JournalClinical Endocrinology
    Volume80
    Issue number2
    DOIs
    StatePublished - Feb 2014

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    Sex Hormone-Binding Globulin
    Estrone
    Testosterone
    Estradiol
    Fluoroimmunoassay
    Independent Living
    Family Relations
    Tandem Mass Spectrometry
    Nuclear Family
    Fathers
    Liquid Chromatography

    All Science Journal Classification (ASJC) codes

    • Endocrinology, Diabetes and Metabolism

    Cite this

    The heritability of circulating testosterone, oestradiol, oestrone and sex hormone binding globulin concentrations in men : The Framingham Heart Study. / Travison, T. G.; Zhuang, W. V.; Lunetta, K. L.; Karasik, D.; Bhasin, S.; Kiel, D. P.; Coviello, A. D.; Murabito, J. M.

    In: Clinical Endocrinology, Vol. 80, No. 2, 02.2014, p. 277-282.

    Research output: Contribution to journalArticle

    Travison, TG, Zhuang, WV, Lunetta, KL, Karasik, D, Bhasin, S, Kiel, DP, Coviello, AD & Murabito, JM 2014, 'The heritability of circulating testosterone, oestradiol, oestrone and sex hormone binding globulin concentrations in men: The Framingham Heart Study', Clinical Endocrinology, vol. 80, no. 2, pp. 277-282. https://doi.org/10.1111/cen.12260
    Travison, T. G. ; Zhuang, W. V. ; Lunetta, K. L. ; Karasik, D. ; Bhasin, S. ; Kiel, D. P. ; Coviello, A. D. ; Murabito, J. M. / The heritability of circulating testosterone, oestradiol, oestrone and sex hormone binding globulin concentrations in men : The Framingham Heart Study. In: Clinical Endocrinology. 2014 ; Vol. 80, No. 2. pp. 277-282.
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    abstract = "Objective Circulating testosterone, oestradiol and oestrone concentrations vary considerably between men. Although a substantial proportion of this variation may be attributed to morbidity and behavioural factors, these cannot account for its entirety, suggesting genetic inheritance as a potential additional determinant. The analysis described here was intended to estimate the heritability of male circulating total testosterone (TT), calculated free testosterone (cFT), oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG), along with the genetic correlation between these factors. Design Cross-sectional, observational analysis of data from male members of the Offspring and Generation 3 cohorts of the Framingham Heart Study. Data were collected in the years 1998-2005. Participants A total of 3367 community-dwelling men contributed to the analysis, including 1066 father/son and 1284 brother pairs among other family relationships. Measurements Levels of serum sex steroids (TT, E1 and E2) were measured by liquid chromatography-tandem mass spectrometry, SHBG by immunofluorometric assay and cFT by mass action equation. Heritability was obtained using variance components analysis with adjustment for covariates including age, diabetes mellitus, body mass index and smoking status. Results Age-adjusted heritability estimates were 0·19, 0·40, 0·40, 0·30 and 0·41 for cFT, TT, E1, E2 and SHBG, respectively. Adjustment for covariates did not substantially attenuate these estimates; SHBG-adjusted TT results were similar to those obtained for cFT. Genetic correlation coefficients (ρG) indicated substantial genetic association between TT and cFT (ρG = 0·68), between TT and SHBG (pG = 0·87), between E1 and E2 (ρG = 0·46) and between TT and E2 (ρG = 0·48). Conclusion Circulating testosterone, oestradiol and oestrone concentrations exhibit substantial heritability in adult men. Significant genetic association between testosterone and oestrogen levels suggests shared genetic pathways.",
    author = "Travison, {T. G.} and Zhuang, {W. V.} and Lunetta, {K. L.} and D. Karasik and S. Bhasin and Kiel, {D. P.} and Coviello, {A. D.} and Murabito, {J. M.}",
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    T1 - The heritability of circulating testosterone, oestradiol, oestrone and sex hormone binding globulin concentrations in men

    T2 - The Framingham Heart Study

    AU - Travison, T. G.

    AU - Zhuang, W. V.

    AU - Lunetta, K. L.

    AU - Karasik, D.

    AU - Bhasin, S.

    AU - Kiel, D. P.

    AU - Coviello, A. D.

    AU - Murabito, J. M.

    PY - 2014/2

    Y1 - 2014/2

    N2 - Objective Circulating testosterone, oestradiol and oestrone concentrations vary considerably between men. Although a substantial proportion of this variation may be attributed to morbidity and behavioural factors, these cannot account for its entirety, suggesting genetic inheritance as a potential additional determinant. The analysis described here was intended to estimate the heritability of male circulating total testosterone (TT), calculated free testosterone (cFT), oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG), along with the genetic correlation between these factors. Design Cross-sectional, observational analysis of data from male members of the Offspring and Generation 3 cohorts of the Framingham Heart Study. Data were collected in the years 1998-2005. Participants A total of 3367 community-dwelling men contributed to the analysis, including 1066 father/son and 1284 brother pairs among other family relationships. Measurements Levels of serum sex steroids (TT, E1 and E2) were measured by liquid chromatography-tandem mass spectrometry, SHBG by immunofluorometric assay and cFT by mass action equation. Heritability was obtained using variance components analysis with adjustment for covariates including age, diabetes mellitus, body mass index and smoking status. Results Age-adjusted heritability estimates were 0·19, 0·40, 0·40, 0·30 and 0·41 for cFT, TT, E1, E2 and SHBG, respectively. Adjustment for covariates did not substantially attenuate these estimates; SHBG-adjusted TT results were similar to those obtained for cFT. Genetic correlation coefficients (ρG) indicated substantial genetic association between TT and cFT (ρG = 0·68), between TT and SHBG (pG = 0·87), between E1 and E2 (ρG = 0·46) and between TT and E2 (ρG = 0·48). Conclusion Circulating testosterone, oestradiol and oestrone concentrations exhibit substantial heritability in adult men. Significant genetic association between testosterone and oestrogen levels suggests shared genetic pathways.

    AB - Objective Circulating testosterone, oestradiol and oestrone concentrations vary considerably between men. Although a substantial proportion of this variation may be attributed to morbidity and behavioural factors, these cannot account for its entirety, suggesting genetic inheritance as a potential additional determinant. The analysis described here was intended to estimate the heritability of male circulating total testosterone (TT), calculated free testosterone (cFT), oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG), along with the genetic correlation between these factors. Design Cross-sectional, observational analysis of data from male members of the Offspring and Generation 3 cohorts of the Framingham Heart Study. Data were collected in the years 1998-2005. Participants A total of 3367 community-dwelling men contributed to the analysis, including 1066 father/son and 1284 brother pairs among other family relationships. Measurements Levels of serum sex steroids (TT, E1 and E2) were measured by liquid chromatography-tandem mass spectrometry, SHBG by immunofluorometric assay and cFT by mass action equation. Heritability was obtained using variance components analysis with adjustment for covariates including age, diabetes mellitus, body mass index and smoking status. Results Age-adjusted heritability estimates were 0·19, 0·40, 0·40, 0·30 and 0·41 for cFT, TT, E1, E2 and SHBG, respectively. Adjustment for covariates did not substantially attenuate these estimates; SHBG-adjusted TT results were similar to those obtained for cFT. Genetic correlation coefficients (ρG) indicated substantial genetic association between TT and cFT (ρG = 0·68), between TT and SHBG (pG = 0·87), between E1 and E2 (ρG = 0·46) and between TT and E2 (ρG = 0·48). Conclusion Circulating testosterone, oestradiol and oestrone concentrations exhibit substantial heritability in adult men. Significant genetic association between testosterone and oestrogen levels suggests shared genetic pathways.

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