Genetically predicted testosterone and cardiovascular risk factors in men: a Mendelian randomization analysis in the Guangzhou Biobank Cohort Study

Jie Zhao, Chaoqiang Jiang, Tai Hing Lam, Bin Liu, Kar Keung Cheng, Lin Xu, Shiu Lun Au Yeung, Weisen Zhang, Gabriel M Leung, C Mary Schooling

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


BACKGROUND: Observationally lower testosterone is associated with an unhealthier cardiovascular (CVD) risk profile, but this association is open to confounding and reverse causality. The authors examined the association of testosterone with well-established cardiovascular disease (CVD) risk factors (blood pressure, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)cholesterol and fasting glucose) and the Framingham score using a Mendelian randomization analysis with a separate-sample instrumental variable estimator.

METHODS: To minimize reverse causality, a genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on three selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). Multivariable censored and linear regressions were used to examine the association of genetically predicted testosterone levels with CVD risk factors and Framingham score among 4212 older Chinese men from the Guangzhou Biobank Cohort Study.

RESULTS: Predicted testosterone was unrelated to systolic blood pressure [-0.11 mmHg, 95% confidence interval (CI) -0.70 to 0.48], diastolic blood pressure (0.04 mmHg, 95% CI -0.27 to 0.36), fasting glucose (0.02 mmol/l, 95% CI -0.02 to 0.06) or Framingham score (0.02, 95% CI -0.0001 to 0.03) but associated with higher LDL-cholesterol (0.02 mmol/l, 95% CI 0.01 to 0.04) and lower HDL-cholesterol (-0.01 mmol/l, 95% CI -0.02 to -0.001), after adjustment for potential confounders (age, education, smoking status, use of alcohol and body mass index).

CONCLUSIONS: Our findings did not corroborate observed protective effects of testosterone on cardiovascular risk factors or risk of ischaemic heart disease among men, but raises the possibility that higher testosterone may be associated with an unhealthier lipid profile.

Original languageEnglish
Pages (from-to)140-8
Number of pages9
JournalInternational Journal of Epidemiology
Issue number1
Publication statusPublished - Feb 2014


  • Adult
  • Aged
  • Aged, 80 and over
  • Asian Continental Ancestry Group
  • Blood Pressure
  • Body Mass Index
  • Cardiovascular Diseases
  • Cholesterol
  • Cohort Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Hong Kong
  • Humans
  • Male
  • Mendelian Randomization Analysis
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Predictive Value of Tests
  • Questionnaires
  • Risk Factors
  • Smoking
  • Socioeconomic Factors
  • Testosterone


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