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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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