title: Genetically predicted testosterone and electrocardiographic QT interval duration in Chinese: a Mendelian randomization analysis in the Guangzhou Biobank Cohort Study.
abstract: BACKGROUND
  QT interval prolongation, a predictor of cardiac arrhythmias, and elevated heart rate are associated with higher risk of cardiovascular mortality. Observationally testosterone is associated with shorter corrected QT interval and slower heart rate; however, the evidence is open to residual confounding and reverse causality. We examined the association of testosterone with electrocardiogram (ECG) parameters using a separate-sample instrumental variable (SSIV) estimator.
  
  
  METHODS
  To minimize reverse causality, a genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on a parsimonious set of single nuclear polymorphisms (rs10046, rs1008805 and rs1256031). Linear regression was used to examine the association of genetically predicted testosterone with QT interval, corrected QT interval [using the Framingham formula (QTf) and Bazett formula (QTb)] and heart rate in 4212 older (50+ years) Chinese men from the Guangzhou Biobank Cohort Study.
  
  
  RESULTS
  Predicted testosterone was not associated with QT interval [-0.08 ms per nmol/l testosterone, 95% confidence interval (CI) -0.81 to 0.65], QTf interval (0.40 ms per nmol/l testosterone, 95% CI -0.12 to 0.93) or heart rate (0.26 beats per minute per nmol/l testosterone, 95% CI -0.04 to 0.56), but was associated with longer QTb interval (0.66 ms per nmol/l testosterone, 95% CI 0.02 to 1.31).
  
  
  CONCLUSIONS
  Our findings do not corroborate observed protective associations of testosterone with QT interval or heart rate among men, but potentially suggest effects in the other direction. Replication in a larger sample is required.
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 School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
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 School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA.
authors.forename: Chaoqiang
authors.initials: C
authors.lastname: Jiang
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 School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA hrmrlth@hku.hk.
authors.forename: Tai Hing
authors.initials: TH
authors.lastname: Lam
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 School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
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 School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA.
authors.forename: Kar Keung
authors.initials: KK
authors.lastname: Cheng
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 School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
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 School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA.
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Long
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 School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA.
authors.forename: Weisen
authors.initials: W
authors.lastname: Zhang
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 School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Leung
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 School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA 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 School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, NY, USA.
authors.forename: C Mary
authors.initials: CM
authors.lastname: Schooling
mesh_terms: D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000235:genetics; D002681:China / Q000208:ethnology; D015331:Cohort Studies; D004562:Electrocardiography; D006339:Heart Rate / Q000235:genetics*; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013739:Testosterone / Q000235:genetics*
chemical_list: D013739:Testosterone; D001141:Aromatase; C561410:CYP19A1 protein, human
keywords: Mendelian randomization; QT interval; testosterone