Alzheimer disease and coronary atherosclerosis: A bidirectional two-sample Mendelian randomization study

SNPs significantly associated with the exposure variables were extracted from the GWAS dataset of the outcome variable to obtain instrumental variables. The inverse-variance weighted (IVW) method was used as the primary approach for causal inference. The MR-Egger method was employed to test for horizontal pleiotropy, while the IVW and MR-Egger methods were used to assess heterogeneity.

A leave-one-out sensitivity analysis was performed to evaluate the robustness of the results.Results When AD was used as the exposure variable and CA as the outcome variable, 5 SNPs (F > 10) were identified, indicating a causal relationship between AD and CA (OR = 3.142, 95% CI: 2.176–4.537, P < 0.001). When CA was used as the exposure variable and AD as the outcome variable, 22 SNPs (F > 10) were identified, but no causal relationship was found between CA and AD (OR = 0.881, 95% CI: 0.454–1.710, P = 0.708).

In both MR analyses, the instrumental variables showed no evidence of horizontal pleiotropy or heterogeneity, and the results were robust.Conclusion Alzheimer's disease has a causal effect on increasing the risk of coronary atherosclerosis, whereas coronary atherosclerosis does not have a causal effect on increasing the risk of Alzheimer's disease.