A Mendelian randomization study of testosterone and cognition in men

Jie V. Zhao; Tai Hing Lam; Chaoqiang Jiang; Stacey S. Cherny; Bin Liu; Kar Keung Cheng; Weisen Zhang; Gabriel M. Leung; C. Mary Schooling

doi:10.1038/srep21306

A Mendelian randomization study of testosterone and cognition in men

Jie V. Zhao, Tai Hing Lam, Chaoqiang Jiang, Stacey S. Cherny, Bin Liu, Kar Keung Cheng, Weisen Zhang, Gabriel M. Leung, C. Mary Schooling

Research output: Contribution to journal › Article › peer-review

Abstract

Testosterone replacement for older men is increasingly common, with some observations suggesting a protective effect on cognitive function. We examined the association of endogenous testosterone with cognitive function among older men in a Mendelian randomization study using a separate-sample instrumental variable (SSIV) analysis estimator to minimize confounding and reverse causality. A genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). The association of genetically predicted testosterone with delayed 10-word recall score and Mini-Mental State Examination (MMSE) score was assessed at baseline and follow-up using generalized estimating equation among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study. Predicted testosterone was not associated with delayed 10-word recall score (-0.02 per nmol/L testosterone, 95% confidence interval (CI) -0.06-0.02) or MMSE score (0.06, 95% CI -0.002-0.12). These estimates were similar after additional adjustment for age, education, smoking, use of alcohol, body mass index and the Framingham score. Our findings do not corroborate observed protective effects of testosterone on cognitive function among older men.

Original language	English
Article number	21306
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep21306
State	Published - 11 Feb 2016
Externally published	Yes

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@article{1d126b4e183e437db65c5e5df347f290,

title = "A Mendelian randomization study of testosterone and cognition in men",

abstract = "Testosterone replacement for older men is increasingly common, with some observations suggesting a protective effect on cognitive function. We examined the association of endogenous testosterone with cognitive function among older men in a Mendelian randomization study using a separate-sample instrumental variable (SSIV) analysis estimator to minimize confounding and reverse causality. A genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). The association of genetically predicted testosterone with delayed 10-word recall score and Mini-Mental State Examination (MMSE) score was assessed at baseline and follow-up using generalized estimating equation among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study. Predicted testosterone was not associated with delayed 10-word recall score (-0.02 per nmol/L testosterone, 95% confidence interval (CI) -0.06-0.02) or MMSE score (0.06, 95% CI -0.002-0.12). These estimates were similar after additional adjustment for age, education, smoking, use of alcohol, body mass index and the Framingham score. Our findings do not corroborate observed protective effects of testosterone on cognitive function among older men.",

author = "Zhao, {Jie V.} and Lam, {Tai Hing} and Chaoqiang Jiang and Cherny, {Stacey S.} and Bin Liu and Cheng, {Kar Keung} and Weisen Zhang and Leung, {Gabriel M.} and Schooling, {C. Mary}",

note = "Funding Information: This work was supported by the University of Hong Kong Foundation for Development and Research (Hong Kong, China); the University of Hong Kong University Research Committee Strategic Research Theme of Public Health (Hong Kong, China); Guangzhou Public Health Bureau (Guangzhou, China; Key technology collaboration project, [grant number 2012J5100041]), Guangzhou Science and Technology Bureau (Guangzhou, China) and the University of Birmingham (Birmingham, United Kingdom). This sub-study was funded by the Research Grant Council General Research Fund [grant number 769710], Research Grant Council of Hong Kong, Hong Kong SAR, People{\textquoteright}s Republic of China.",

year = "2016",

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doi = "10.1038/srep21306",

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journal = "Scientific Reports",

issn = "2045-2322",

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AU - Cheng, Kar Keung

AU - Zhang, Weisen

AU - Leung, Gabriel M.

AU - Schooling, C. Mary

N1 - Funding Information: This work was supported by the University of Hong Kong Foundation for Development and Research (Hong Kong, China); the University of Hong Kong University Research Committee Strategic Research Theme of Public Health (Hong Kong, China); Guangzhou Public Health Bureau (Guangzhou, China; Key technology collaboration project, [grant number 2012J5100041]), Guangzhou Science and Technology Bureau (Guangzhou, China) and the University of Birmingham (Birmingham, United Kingdom). This sub-study was funded by the Research Grant Council General Research Fund [grant number 769710], Research Grant Council of Hong Kong, Hong Kong SAR, People’s Republic of China.

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N2 - Testosterone replacement for older men is increasingly common, with some observations suggesting a protective effect on cognitive function. We examined the association of endogenous testosterone with cognitive function among older men in a Mendelian randomization study using a separate-sample instrumental variable (SSIV) analysis estimator to minimize confounding and reverse causality. A genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). The association of genetically predicted testosterone with delayed 10-word recall score and Mini-Mental State Examination (MMSE) score was assessed at baseline and follow-up using generalized estimating equation among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study. Predicted testosterone was not associated with delayed 10-word recall score (-0.02 per nmol/L testosterone, 95% confidence interval (CI) -0.06-0.02) or MMSE score (0.06, 95% CI -0.002-0.12). These estimates were similar after additional adjustment for age, education, smoking, use of alcohol, body mass index and the Framingham score. Our findings do not corroborate observed protective effects of testosterone on cognitive function among older men.

AB - Testosterone replacement for older men is increasingly common, with some observations suggesting a protective effect on cognitive function. We examined the association of endogenous testosterone with cognitive function among older men in a Mendelian randomization study using a separate-sample instrumental variable (SSIV) analysis estimator to minimize confounding and reverse causality. A genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). The association of genetically predicted testosterone with delayed 10-word recall score and Mini-Mental State Examination (MMSE) score was assessed at baseline and follow-up using generalized estimating equation among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study. Predicted testosterone was not associated with delayed 10-word recall score (-0.02 per nmol/L testosterone, 95% confidence interval (CI) -0.06-0.02) or MMSE score (0.06, 95% CI -0.002-0.12). These estimates were similar after additional adjustment for age, education, smoking, use of alcohol, body mass index and the Framingham score. Our findings do not corroborate observed protective effects of testosterone on cognitive function among older men.

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A Mendelian randomization study of testosterone and cognition in men

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