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Cohort study
Mendelian randomisation meta-analysis sheds doubt on protective associations between ‘moderate’ alcohol consumption and coronary heart disease
  1. Tanya N Chikritzhs1,
  2. Timothy S Naimi2,
  3. Tim R Stockwell3,
  4. Wenbin Liang1
  1. 1National Drug Research Institute, Curtin University, Perth, Western Australia, Australia;
  2. 2Section of General Internal Medicine, Boston University Medical Center, Boston, Massachusetts, USA;
  3. 3Centre for Addictions Research of British Columbia, University of Victoria, Victoria, British Columbia, Canada
  1. Correspondence to : Professor Tanya N Chikritzhs, National Drug Research Institute, Curtin University, GPO Box U1987, Perth, WA 6845, Australia; t.n.chikritzhs{at}

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A protective association between low-dose alcohol and risk of coronary heart disease (CHD) has been suggested by meta-analyses of observational studies and experimental studies. Observational studies are, however, vulnerable to residual confounding and selection bias. Compared with observational studies, the Mendelian randomisation (MR) approach can mitigate confounding, is immune to reverse causation, and is consistent with intention-to-treat principles since ‘quitting’ a genotype is impossible.


The MR approach relies on the random assignment of genetic variants (genotypes) at meiosis to randomly allocate participants to exposures (eg, alcohol consumption) known to be affected by those genotypes. Holmes and colleagues applied an MR meta-analysis design to data from 56 studies, including 260 000 participants of European ancestry. A variant …

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