title: Alcohol Use and Gamma-Glutamyltransferase Using a Mendelian Randomization Design in the Guangzhou Biobank Cohort Study.
abstract: BACKGROUND
  Observational studies and small intervention studies suggest alcohol raises gamma-glutamyltransferase (GGT). We used Mendelian randomization to assess the causal effect of alcohol use on GGT in older Chinese people.
  
  
  METHODS
  An instrumental variable (IV) analysis in 2,321 men and 2,757 women aged 50+ years from phase 3 of the Guangzhou Biobank Cohort Study with ALDH2 (rs671) genotyped, alcohol use and GGT available was used to assess the causal effect of alcohol use on GGT. Rs671 was used as an IV and F-statistics was used to test for weak instrument hypothesis. An F-statistic of ≥10 indicates the IV is not weak.
  
  
  RESULTS
  In men, the F-statistic for rs671 on alcohol use was 70. Using IV analysis alcohol use increased GGT by 10.60 U/L per alcohol unit (10 gram ethanol) per day (95% confidence interval (CI) 6.58 to 14.62). The estimate was lower in observational multivariate regression: 3.48 U/L GGT per alcohol unit per day (95% CI 2.84 to 4.11) adjusted for age, education, physical activity and smoking. In women, rs671 was not associated with alcohol or GGT and the F-statistic was 7 precluding IV analysis.
  
  
  CONCLUSIONS
  In Mendelian randomization, we found confirmative evidence that alcohol use increases GGT among Southern Chinese men. Moreover, we found that the ALDH2 variant rs671 was not associated with GGT among Southern Chinese women who generally consume very low levels of alcohol. Taken together our findings strongly suggest that alcohol increases GGT, although we cannot rule out the possibility that other unknown factors may cause a different relation between alcohol and GGT in other populations.
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Guangzhou No.12 Hospital, Guangzhou, 510620, China.
authors.forename: Chao Qiang
authors.initials: CQ
authors.lastname: Jiang
authors.affiliation: Public Health, Epidemiology and Biostatistics, University of Birmingham, Birmingham, UK.
authors.forename: Kar Keung
authors.initials: KK
authors.lastname: Cheng
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Shiu Lun Ryan
authors.initials: SL
authors.lastname: Au Yeung
authors.affiliation: Guangzhou No.12 Hospital, Guangzhou, 510620, China.
authors.forename: Wei Sen
authors.initials: WS
authors.lastname: Zhang
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Tai Hing
authors.initials: TH
authors.lastname: Lam
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; School of Urban Public Health, Hunter College and CUNY School of Public Health, New York, New York, United States of America.
authors.forename: Catherine Mary
authors.initials: CM
authors.lastname: Schooling
mesh_terms: D000368:Aged; D000428:Alcohol Drinking; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D002681:China; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012959:Socioeconomic Factors; D005723:gamma-Glutamyltransferase / Q000097:blood / Q000235:genetics* / Q000378:metabolism*
chemical_list: C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D005723:gamma-Glutamyltransferase