An investigator uses single nucleotide polymorphisms in the alcohol dehydrogenase gene, randomly allocated at meiosis, as instruments to estimate the effect of alcohol intake on blood pressure. The main methodological advantage of this approach over a conventional observational cohort is:

• A It eliminates the need for a large sample size
• B It directly proves causation without any assumptions
• C Genetic variants are largely free of confounding and reverse causation ✓
• D It measures short-term alcohol intake more accurately than self-report

Explanation

Mendelian randomization exploits the random assortment of alleles at conception, mimicking the allocation of a randomized trial. Because germline variants are fixed at conception and generally unrelated to environmental confounders, and because outcome cannot alter genotype, both confounding and reverse causation are minimized. Option B is wrong because validity still depends on assumptions such as no pleiotropy. Sample size needs are typically larger, and genotyping does not improve measurement of current intake.

Reference: Modern Epidemiology, Rothman, as reviewed in standard PSM texts ed.

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