title: Is aldehyde dehydrogenase 2 a credible genetic instrument for alcohol use in Mendelian randomization analysis in Southern Chinese men?
abstract: BACKGROUND
  Mendelian randomization studies provide a means of assessing causal relations without interventions, but require valid genetic instruments. We assessed the credibility of aldehyde dehydrogenase 2 (ALDH2) as a genetic instrument for alcohol use in Southern Chinese men.
  
  
  METHODS
  We genotyped the single nucleotide polymorphism rs671 of ALDH2 in 4867 men from the Guangzhou Biobank Cohort Study. We used linear regression to assess the strength of the association of ALDH2 variants with alcohol use, whether ALDH2 variants were independently associated with socio-economic position or other potential confounders and whether associations of ALDH2 variants with cardiovascular risk factors (systolic and diastolic blood pressure, HDL- and LDL-cholesterol, fasting glucose), triglycerides, body mass index, self reported cardiovascular disease, self-reported ischaemic heart disease, cognitive function (delayed 10-word recall and Mini Mental State Examination score) and liver function (alanine transaminase and aspartate transaminase) were fully mediated by alcohol use.
  
  
  RESULTS
  The minor allele frequency (A) of ALDH2 was 0.29. The F statistic for ALDH2 variants was 75.0, suggesting that substantial weak instrument bias is unlikely. ALDH2 variants were not associated with socio-economic position, smoking or physical activity. ALDH2 variants were only associated with diastolic blood pressure and HDL-cholesterol, but these genetic associations with blood pressure and HDL-cholesterol were attenuated after adjusting for alcohol use, suggesting the apparent genetic associations were possibly mediated by alcohol use.
  
  
  CONCLUSIONS
  ALDH2 variants are a credible genetic instrument for Mendelian randomization studies of alcohol use and many attributes of health in Southern Chinese men.
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: 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 / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012959:Socioeconomic Factors
chemical_list: C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial