Investigation of Causal Effect of Atrial Fibrillation on Alzheimer Disease: A Mendelian Randomization Study

Figures

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  Figure 1. Conceptual framework for the Mendelian randomization analysis of atrial fibrillation and risk of Alzheimer disease. The design is under the assumption that the genetic variants are associated with atrial fibrillation, but not with confounders, and the genetic variants are not associated with risk of Alzheimer disease conditional on atrial fibrillation and confounders. SNP indicates single nucleotide polymorphism.

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  Figure 2. Risk of Alzheimer disease for genetically predicted atrial fibrillation. IVW indicates inverse‐variance weighted; MBE, mode‐based estimate; MR, Mendelian randomization; MR‐PRESSO, Mendelian Randomization Pleiotropy RESidual Sum and Outlier.

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  Figure 3. Associations of atrial fibrillation–related variants with risk of Alzheimer disease. The red line indicates the estimate of effect using inverse‐variance weighted method. Circles indicate marginal genetic associations with atrial fibrillation and risk of Alzheimer disease for each variant. Error bars indicate 95% CIs.

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  Figure 4. Funnel plot of the Mendelian randomization analysis for Alzheimer disease. Funnel plot evaluated the presence of possible heterogeneity across the estimates, which indicates the potential pleiotropic effects. The figure presents the observed causal effect of each of the 93 instrumental variables (IVs) by dots, and the averaged causal effect of all IVs combined (βIV) using inverse variance weighted (solid line) and MR‐Egger (dashed line) method on x‐axis. Y axis presents the inverse standard error of the estimated causal effect for each of the single nucleotide polymorphisms (IVs).

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  Figure 5. MR leave‐1‐out sensitivity analysis for atrial fibrillation on AD. Circles indicate MR estimates for atrial fibrillation on Alzheimer disease using inverse‐variance weighted fixed‐effect method if the SNP was omitted. The bars indicate the CI of MR estimates. AD indicates Alzheimer disease; AF, atrial fibrillation; MR, Mendelian randomization.