A Mendelian Randomization study uses genetic variants as instrumental variables to test the causal effect of LDL cholesterol on cardiovascular disease. Which property of the genetic variant is ESSENTIAL for it to be a valid instrumental variable?

• A It must be strongly associated with the outcome (cardiovascular disease)
• B It must be in Hardy-Weinberg equilibrium in cases
• C It must be associated with the exposure (LDL), independent of confounders, and affect the outcome only through LDL ✓
• D It must cause complete penetrance of high LDL levels

Explanation

For a genetic variant to serve as a valid instrumental variable in Mendelian Randomization, three assumptions must hold: (1) relevance — the variant must be strongly associated with the exposure (LDL); (2) independence — the variant must not be associated with confounders; (3) exclusion restriction — the variant must affect the outcome (CVD) ONLY through the exposure (LDL), not through other pathways (no pleiotropy). These three conditions together justify causal inference.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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