Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.

Article, 0038 English OPEN
Holmes, M. V. ; Dale, C. E. ; Zuccolo, L. ; Silverwood, R. J. ; Guo, Y. ; Ye, Z. ; Prieto-Merino, D. ; Dehghan, A. ; Trompet, S. ; Wong, A. ; Cavadino, A. ; Drogan, D. ; Padmanabhan, S. ; Li, S. ; Yesupriya, A. ; Leusink, M. ; Sundstrom, J. ; Hubacek, J. A. ; Pikhart, H. ; Swerdlow, D. I. ; Panayiotou, A. G. ; Borinskaya, S. A. ; Finan, C. ; Shah, S. ; Kuchenbaecker, K. B. ; Shah, T. ; Engmann, J. ; Folkersen, L. ; Eriksson, P. ; Ricceri, F. ... view all 156 authors (2014)
  • Publisher: BMJ Publishing Group Ltd.
  • Journal: The BMJ (issn: 0959-8138, vol: 349)
  • Related identifiers: pmc: PMC4091648, doi: 10.1136/bmj.g4164., doi: 10.1136/bmj.g4164
  • Subject: Kardiologi | Models, Statistical | RISK-FACTORS | Alcohol Dehydrogenase | Mendelian Randomization Analysis | VARIANTS | DEHYDROGENASE | Research | Coronary Disease | 616.1 [udc] | Polymorphism, Single Nucleotide | DESIGN | CORONARY-HEART-DISEASE | DEPENDENCE | Cardiac and Cardiovascular Systems | Female | Alcohol drinking ; Adverse effects ; Alcoholism ; Epidemiology ; Cardiovascular diseases ; Epidemiology ; Regression analysis ; Meta-analysis as topic | METAANALYSIS | Aged | HEALTH | CONSUMPTION | Middle Aged | Stroke | Alcohol Drinking | Genotype | Biological Markers | MORTALITY | Adult; Aged; Alcohol Dehydrogenase/genetics; Alcohol Drinking/adverse effects; Alcohol Drinking/genetics; Biomarkers/blood; Coronary Disease/blood; Coronary Disease/etiology; Coronary Disease/genetics; Female; Genetic Markers; Genotype; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Models, Statistical; Polymorphism, Single Nucleotide; Stroke/blood; Stroke/etiology; Stroke/genetics | Adult | Genetic Markers | Humans | Male

Objective: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.<p></p>\ud \ud Design: Mendelian randomisation meta-analysis of 56 epidemiological studies.<p></p>\ud \ud Participants: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers.<p></p>\ud \ud Main outcome measures: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.<p></p>\ud \ud Results: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (−0.88 (−1.19 to −0.56) mm Hg), interleukin-6 levels (−5.2% (−7.8 to −2.4%)), waist circumference (−0.3 (−0.6 to −0.1) cm), and body mass index (−0.17 (−0.24 to −0.10) kg/m2). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)).<p></p>\ud \ud Conclusions: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.