ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- A multi-ancestry polygenic risk score for Alzheimer disease is associated with cognitive decline, hippocampal atrophy and neuropathological hallmarks in diverse populations.medRxiv : the preprint server for health sciences · 2025Article
- Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
Corrections and comments
- Erratum issued
- Update of
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27 authors.
Funding
Abstract
introductionIdentifying pleiotropy for blood pressure (BP) and cognitive performance measures may indicate mechanistic links between hypertension and Alzheimer's disease (AD).
methodsWe performed a pleiotropy genome-wide association study (GWAS) for paired measures of systolic, diastolic, pulse, and mean arterial pressure with memory, executive function, and language scores using 116,075 exam data from 25,726 participants in clinic-based and prospective cohorts. Significant findings were evaluated by Bayesian colocalization and differential gene expression in brain tissue from pathologically confirmed AD cases with and without clinical symptoms.
resultsGenome-wide significant pleiotropy for BP and cognitive performance with JPH2, GATA3, PAX2, LOC105371656, and SUFU in the total sample; RTN4, ULK2, SORBS2, and LOC100128993 in prospective cohorts; and ADAMTS3 and LINC02946 in clinic-based cohorts. Six pleiotropic loci influence cognition directly, and six genes were differentially expressed between pathologically confirmed AD cases with and without antemortem cognitive impairment. DISCUSSION: Our results provide insight into mechanisms underlying hypertension and AD. HIGHLIGHTS: Genome-wide significant pleiotropy in blood pressure (BP) and cognitive performance measures were identified with 11 novel loci: JPH2, GATA3, PAX2, LOC105371656, SUFU in the total sample; RTN4, ULK2, SORBS2, LOC100128993 in prospective cohorts; and ADAMTS3, LINC02946 in clinic-based cohorts. SUFU, RTN4, SORBS2, ADAMTS3, and GATA3 affected cognition directly rather than through BP. ACTR1A, HIF1AN, ADAMTS3, RTN4, SORBS2, and SUFU at pleiotropic loci were differentially expressed among controls and pathologically confirmed AD cases with and without clinical symptoms.
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