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Chunk #21 — Methods — Examples

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Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression.
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To demonstrate this approach for the assessment of directional pleiotropy, we consider two illustrative examples of Mendelian randomization using many genetic variants that have been recently published. We use the available data on genetic associations with the exposure and with the outcome to construct a funnel plot and perform a visual inspection for asymmetry, as well as a formal statistical test using MR-Egger regression. We comment on the differences between the IVW causal effect estimate from equation (3), which assumes that all the genetic variants are valid IVs, and the MR-Egger estimate from equation (4), which makes assumptions IV1, IV2 and the InSIDE assumption.