title: Moderate alcohol use and cardiovascular disease from Mendelian randomization.
abstract: BACKGROUND
  Observational studies show moderate alcohol use negatively associated with ischemic heart disease (IHD) and cardiovascular disease (CVD). However, healthier attributes among moderate users compared to never users may confound the apparent association. A potentially less biased way to examine the association is Mendelian randomization, using alcohol metabolizing genes which influence alcohol use.
  
  
  METHODS
  We used instrumental variable analysis with aldehyde dehydrogenase 2 (ALDH2) genotypes (AA/GA/GG) as instrumental variables for alcohol use to examine the association of alcohol use (10 g ethanol/day) with CVD risk factors (blood pressure, lipids and glucose) and morbidity (self-reported IHD and CVD) among men in the Guangzhou Biobank Cohort Study.
  
  
  RESULTS
  ALDH2 genotypes were a credible instrument for alcohol use (F-statistic 74.6). Alcohol was positively associated with HDL-cholesterol (0.05 mmol/L per alcohol unit, 95% confidence interval (CI) 0.02 to 0.08) and diastolic blood pressure (1.15 mmHg, 95% CI 0.23 to 2.07) but not with systolic blood pressure (1.00 mmHg, 95% CI -0.74 to 2.74), LDL-cholesterol (0.03 mmol/L, 95% CI -0.03 to 0.08), log transformed triglycerides (0.03 mmol/L, 95% CI -0.01 to 0.08) or log transformed fasting glucose (0.01 mmol/L, 95% CI -0.006 to 0.03), self-reported CVD (odds ratio (OR) 0.98, 95% CI 0.76 to 1.27) or self-reported IHD (OR 1.10, 95% CI 0.83 to 1.45).
  
  
  CONCLUSIONS
  Low to moderate alcohol use among men had the expected effects on most CVD risk factors but not fasting glucose. Larger studies are needed to confirm the null associations with IHD, CVD and fasting glucose.
authors.affiliation: Lifestyle and Lifecourse Epidemiology Group, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Shiu Lun
authors.initials: SL
authors.lastname: Au Yeung
authors.forename: Chaoqiang
authors.initials: C
authors.lastname: Jiang
authors.forename: Kar Keung
authors.initials: KK
authors.lastname: Cheng
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Cowling
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Weisen
authors.initials: W
authors.lastname: Zhang
authors.forename: Tai Hing
authors.initials: TH
authors.lastname: Lam
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Leung
authors.forename: C Mary
authors.initials: CM
authors.lastname: Schooling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000097:blood*; D000444:Aldehyde Dehydrogenase / Q000097:blood / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000097:blood; D005215:Fasting / Q000097:blood; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial