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

A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to examine the causal relationship between Alzheimer's disease (AD) and coronary atherosclerosis (CA).Methods Genome-wide association study (GWAS) datasets for AD and CA were extracted from GWAS databases. AD and CA were alternately treated as exposure and outcome variables in the MR analysis. Single nucleotide polymorphisms (SNPs) significantly associated with the exposure variables were selected using the thresholds of P < 5.0×10-8, r2 < 0.001, and a genetic distance of 10,000 kb. 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.