A Mendelian randomization study uses single nucleotide polymorphisms (SNPs) as instrumental variables for estimating causal effects of an exposure. This design is preferred over observational studies because SNPs:

• A Directly measure phenotypic exposure better than questionnaire data
• B Are randomly allocated at conception and are not confounded by lifestyle or environmental factors ✓
• C Eliminate measurement error in the outcome completely
• D Allow adjustment for time-varying confounders better than propensity scores

Explanation

Mendelian randomization exploits the random assortment of alleles at conception (analogous to randomization in an RCT) so that SNPs associated with the exposure are allocated independently of confounders — a phenomenon called 'Mendelian randomization.' Since genetic variants are fixed at conception and cannot be altered by lifestyle, reverse causation is also avoided. For valid MR, the SNP must: (1) be associated with the exposure, (2) affect the outcome only through the exposure (exclusion restriction), and (3) be independent of confounders. It does not eliminate measurement error in outcomes, nor does it outperform propensity scores for time-varying confounders.

Reference: Park's Textbook of Preventive and Social Medicine, 27th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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