ArticlemedRxiv : the preprint server for health sciences2025
Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures.
Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Genome-wide association studies (GWAS) have identified over 1,000 blood pressure (BP) loci and over 80 loci for Alzheimer's disease (AD). Considering BP is an AD risk factor, identifying pleiotropy in BP and cognitive performance measures may indicate mechanistic links between BP and AD. Methods: Genome-wide scans for pleiotropy in BP variables-systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse pressure (PP)-and co-calibrated scores for cognitive domains (executive function, language, and memory) were performed using generalized linear mixed models and 116,075 longitudinal measures from 25,726 participants of clinic-based and prospective cohorts. GWAS was conducted using PLACO to estimate each SNP's main effect and interaction with age, and their joint effect on pleiotropy. Effects of genome-wide significant (GWS) pleiotropic SNPs on cognition as direct or mediated through BP were evaluated using Mendelian randomization. Potential contribution of genes in top-ranked pleiotropic loci to cognitive resilience was assessed by comparing their expression in brain tissue from pathologically confirmed AD cases with and without clinical symptoms. Results: Pleiotropy GWAS identified GWS associations with Conclusion: Our results provide insight into the underlying mechanisms of high BP and AD. Ongoing efforts to harmonize BP and cognitive measures across several cohorts will improve the power of discovering, replicating, and generalizing novel associations with pleiotropic loci.
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