Relationship between diastolic blood pressure and Alzheimer disease: A 2-sample Mendelian randomization study based...

This study investigates the causal relationship between diastolic blood pressure (DBP) and Alzheimer disease (AD) using 2-sample Mendelian randomization (MR) analysis with publicly available genome-wide association study (GWAS) data and empirical validation. Automated screening identified DBP as a factor related to AD. Two-sample MR analyses were conducted using inverse variance weighting (IVW), MR-Egger regression, weighted median, simple mode, and weighted mode methods. Tests for pleiotropy, heterogeneity, and stability of genetic variants were performed. Data included DBP from Europeans (n = 422,713) and AD cases (n = 753) and controls (n = 736) of European ancestry. An empirical sample of 125 patients with cardiovascular disease in Chinese was used to verify the possibility of the above relationship by restricted cubic spline method. Thirty-seven genome-wide significant nucleotide polymorphisms from DBP GWAS were used as instrumental variables. IVW showed a causal relationship between DBP and AD (β = -1.594, SE = 0.580, P = .006). MR-Egger regression indicated minimal pleiotropy (intercept = 0.037; P = .736) and confirmed the causal relationship (β = -3.110, SE = 1.376, P = .030). The weighted median method also supported this relationship (β = -1.868, SE = 0.856, P = .029). The simple and weighted mode methods did not find significant relationships (P > .1). No heterogeneity or asymmetry was detected by Cochran Q test or the funnel plot, and the leave-one-out method showed stable results. The validation results indicate that the aforementioned findings are stable within the normal range of DBP. MR analysis supports a potential causal link between higher DBP and a lower risk of AD. The screening exposure method used could enhance MR study efficiency.