title: Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.
abstract: 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.
  
  
  METHODS
  Mendelian randomisation meta-analysis of 56 epidemiological studies.
  
  
  METHODS
  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.
  
  
  METHODS
  Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.
  
  
  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/m(2)). 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)).
  
  
  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.
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authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.affiliation: Division of Sleep and Circadian Disorders, Brigham and Women's Hospital; Harvard Medical School, Boston USA Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Patel
authors.affiliation: Division of Sleep and Circadian Disorders, Brigham and Women's Hospital; Harvard Medical School, Boston USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.affiliation: National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Johnson
authors.affiliation: Baylor College of Medicine, Department of Medicine, Division of Atherosclerosis & Vascular Medicine, Houston, Texas 77030, USA.
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, USA.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, Calif, USA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Division of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston, Texas, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK.
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Asselbergs
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Naveed
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authors.lastname: Sattar
authors.affiliation: MRC Integrative Epidemiology Unit (IEU) at the Universty of Bristol, Oakfield House, Bristol BS8 2BN, UK.
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK Genetics, R&D, GlaxoSmithKline, Stevenage, UK.
authors.forename: John
authors.initials: J
authors.lastname: Whittaker
authors.affiliation: MRC Integrative Epidemiology Unit (IEU) at the Universty of Bristol, Oakfield House, Bristol BS8 2BN, UK.
authors.forename: George
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authors.lastname: Davey Smith
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Kenneth
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authors.lastname: Mukamal
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authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
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authors.initials: JG
authors.lastname: Wilson
authors.affiliation: Department of Genetics, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, North Carolina 27514, USA.
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authors.initials: LA
authors.lastname: Lange
authors.affiliation: College of Pharmacy, The University of New Mexico, Albuquerque, NM, USA.
authors.forename: Ajna
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authors.affiliation: Genetic Epidemiology Group, Institute of Cardiovascular Science, Department of Epidemiology and Public Health, University College London, UK.
authors.forename: Aroon D
authors.initials: AD
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authors.affiliation: The Copenhagen General Population Study, Herlev Hospital, Copenhagen, Denmark Faculty of Health Sciences, Copenhagen University Hospital, University of Copenhagen,Copenhagen, Denmark Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, UK.
authors.forename: Martin
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authors.lastname: Bobak
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.
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authors.lastname: Leon
authors.affiliation: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Langenberg
authors.affiliation: Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Tom M
authors.initials: TM
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authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
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authors.initials: AP
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authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Keating
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Dudbridge
authors.affiliation: Genetic Epidemiology Group, Institute of Cardiovascular Science, Department of Epidemiology and Public Health, University College London, UK Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK Juan-P.Casas@lshtm.ac.uk.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Casas
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000209:etiology* / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000097:blood / Q000209:etiology* / Q000235:genetics
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase