title: Exploring causal associations between alcohol and coronary heart disease risk factors: findings from a Mendelian randomization study in the Copenhagen General Population Study.
abstract: OBJECTIVE
  To explore the causal effect of long-term alcohol consumption on coronary heart disease risk factors.
  
  
  RESULTS
  We used variants in ADH1B and ADH1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on body mass index (BMI), blood pressure (BP), lipids, fibrinogen, and glucose. Analyses were undertaken in 54 604 Danes (mean age 56 years). Both confounder-adjusted multivariable and IV analyses suggested that a greater alcohol consumption among those who drank any alcohol resulted in a higher BP [mean difference in SBP per doubling of alcohol consumption among drinkers: 0.76 mmHg (95% CI: 0.63, 0.90) from multivariable analyses and 0.94 mmHg (-3.03, 4.69) from IV analyses; P-value for difference in these results = 0.95]. The positive association of alcohol with HDLc in the multivariable analyses [4.9% (4.7, 5.1)] appeared stronger than in the IV analyses [1.5% (-4.5, 7.4)], and the weak inverse association with fibrinogen in the multivariable analysis [-2.0% (-2.1, -1.8)] was not present in the IV analyses [0.6% (-3.8, 5.0)], but statistically the results for both of these could not be reliably distinguished from each other (P-values 0.21 and 0.32, respectively). The weak inverse association of alcohol with BMI [-0.13 kg/m(2) (-0.16, -0.10)] and with triglycerides [-0.4% (-0.7, 0.4)] in multivariable analyses were in contrast to the strong positive association of alcohol with BMI [1.37 kg/m(2) (0.59, 2.15)] and the strong inverse association with triglycerides [-14.9% (-25.6, -4.3)] in IV analyses; P = 0.006 and 0.01, respectively, for difference between the two. Alcohol was not associated with non-HDLc or glucose.
  
  
  CONCLUSIONS
  Our results show adverse effects of long-term alcohol consumption on BP and BMI. We also found novel evidence for a potentially beneficial effect on triglyceride levels, which needs further replication.
authors.affiliation: MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, BS8 2BN Bristol, UK. d.a.lawlor@bristol.ac.uk
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.forename: Marianne
authors.initials: M
authors.lastname: Benn
authors.forename: Luisa
authors.initials: L
authors.lastname: Zuccolo
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjaerg-Hansen
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000453:epidemiology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D008055:Lipids; D005340:Fibrinogen; C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase
keywords: ADH1B; ADH1C genes; Alcohol; Blood pressure; Fibrinogen; Glucose; Lipids