title: Genetically predicted testosterone and cardiovascular risk factors in men: a Mendelian randomization analysis in the Guangzhou Biobank Cohort Study.
abstract: 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.
authors.affiliation: School of Public Health, The University of Hong Kong, Hong Kong SAR, China, Guangzhou Number 12 Hospital, Guangzhou, China, Department of Public Health and Epidemiology, University of Birmingham, Birmingham, UK and CUNY School of Public Health and Hunter College, New York, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Chaoqiang
authors.initials: C
authors.lastname: Jiang
authors.forename: Tai Hing
authors.initials: TH
authors.lastname: Lam
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Kar Keung
authors.initials: KK
authors.lastname: Cheng
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Shiu Lun
authors.initials: SL
authors.lastname: Au Yeung
authors.forename: Weisen
authors.initials: W
authors.lastname: Zhang
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Leung
authors.forename: C Mary
authors.initials: CM
authors.lastname: Schooling
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D012959:Socioeconomic Factors; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000097:blood / Q000235:genetics*
chemical_list: D013739:Testosterone; D002784:Cholesterol
keywords: Mendelian randomization; cardiovascular disease; cholesterol; risk factors; testosterone