ArticleAlzheimer's research & therapy2021
Multi-trait association studies discover pleiotropic loci between Alzheimer's disease and cardiometabolic traits.
Article in Alzheimer's research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Genome wide association study meta-analysis of neuropathologic lesions of Alzheimer's disease and related dementias in a multi-site autopsy cohort.PLoS genetics · 2026Pooled it
- A genome-wide search for pleiotropy in more than 100,000 harmonized longitudinal cognitive domain scores.Molecular neurodegeneration · 2023Pooled it
- PhenoMapR: scalable mapping of sample phenotypes to single-cell, spatial, and bulk transcriptomics data.bioRxiv : the preprint server for biology · 2026Article
- "Comprehensive multi-omics of age-respective plasma and matrix-bound extracellular vesicles identifies anti-fibrotic miRNAs validated on a heart-on-a-chip".Biomaterials · 2026Article
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- Unraveling COPD pathogenesis: a multi-omics approach to identify metabolites and genetic links.Scientific reports · 2026Article
- A machine learning framework for classifying dementia risk in mild cognitive impairment: evidence from a Korean genome-wide association study cohort.Alzheimer's research & therapy · 2025Article
- Causality of genetically determined gut microbiota on lung cancer: a Mendelian randomization study.Journal of thoracic disease · 2025Article
- Amyloid-beta metabolism in age-related neurocardiovascular diseases.European heart journal · 2025Review
- Single-microglia transcriptomic transition network-based prediction and real-world patient data validation identifies ketorolac as a repurposable drug for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Is the Relationship Between Cardiovascular Disease and Alzheimer's Disease Genetic? A Scoping Review.Genes · 2024Article
- Risk of Alzheimer's disease and genetically predicted levels of 1400 plasma metabolites: a Mendelian randomization study.Scientific reports · 2024Article
- Modern Plant Breeding Techniques in Crop Improvement and Genetic Diversity: From Molecular Markers and Gene Editing to Artificial Intelligence-A Critical Review.Plants (Basel, Switzerland) · 2024Review
- Cross-phenotype associations between Alzheimer's Disease and its comorbidities may provide clues to progression.AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2024Article
- Cross-phenotype associations between Alzheimer's Disease and its comorbidities may provide clues to progression.medRxiv : the preprint server for health sciences · 2023Article
- Article
- Altered blood gene expression in the obesity-related type 2 diabetes cluster may be causally involved in lipid metabolism: a Mendelian randomisation study.Diabetologia · 2023Article
- Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation.Cell death discovery · 2023Article
- Genome-wide cross-trait analysis and Mendelian randomization reveal a shared genetic etiology and causality between COVID-19 and venous thromboembolism.Communications biology · 2023Article
- Article
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundIdentification of genetic risk factors that are shared between Alzheimer's disease (AD) and other traits, i.e., pleiotropy, can help improve our understanding of the etiology of AD and potentially detect new therapeutic targets. Previous epidemiological correlations observed between cardiometabolic traits and AD led us to assess the pleiotropy between these traits.
methodsWe performed a set of bivariate genome-wide association studies coupled with colocalization analysis to identify loci that are shared between AD and eleven cardiometabolic traits. For each of these loci, we performed colocalization with Genotype-Tissue Expression (GTEx) project expression quantitative trait loci (eQTL) to identify candidate causal genes.
resultsWe identified three previously unreported pleiotropic trait associations at known AD loci as well as four novel pleiotropic loci. One associated locus was tagged by a low-frequency coding variant in the gene DOCK4 and is potentially implicated in its alternative splicing. Colocalization with GTEx eQTL data identified additional candidate genes for the loci we detected, including ACE, the target of the hypertensive drug class of ACE inhibitors. We found that the allele associated with decreased ACE expression in brain tissue was also associated with increased risk of AD, providing human genetic evidence of a potential increase in AD risk from use of an established anti-hypertensive therapeutic.
conclusionOur results support a complex genetic relationship between AD and these cardiometabolic traits, and the candidate causal genes identified suggest that blood pressure and immune response play a role in the pleiotropy between these traits.
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