An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene
Year: 2020
Type: article
Study design: Observational Study
Abstract: A growing number of epigenome-wide association studies have demonstrated a role for DNA methylation in the brain in Alzheimer's disease. With the aim of exploring peripheral biomarker potential, we have examined DNA methylation patterns in whole blood collected from 284 individuals in the AddNeuroMed study, which included 89 nondemented controls, 86 patients with Alzheimer's disease, and 109 individuals with mild cognitive impairment, including 38 individuals who progressed to Alzheimer's disease within 1 year. We identified significant differentially methylated regions, including 12 adjacent hypermethylated probes in the HOXB6 gene in Alzheimer's disease, which we validated using pyrosequencing. Using weighted gene correlation network analysis, we identified comethylated modules of genes that were associated with key variables such as APOE genotype and diagnosis. In summary, this study represents the first large-scale epigenome-wide association study of Alzheimer's disease and mild cognitive impairment using blood. We highlight the differences in various loci and pathways in early disease, suggesting that these patterns relate to cognitive decline at an early stage.
Source: Neurobiology of Aging
Authors: Janou A.Y. Roubroeks, Adam R. Smith, Rebecca G. Smith, Ehsan Pishva, Zina Ibrahim, Martina Sattlecker, Eilis J. Hannon, Iwona Kłoszewska, Patrizia Mecocci, Hilkka Soininen, Magda Tsolaki, Bruno Vellas, Lars-Olof Wahlund, Dag Aarsland, Petroula Proitsi, Angela Hodges, Simon Lovestone, Stephen J. Newhouse, Richard J.B. Dobson, Jonathan Mill, Daniël L.A. van den Hove, Katie Lunnon
Institutions: University of Exeter, Maastricht University, King's College London, Farr Institute, University College London, Medical University of Lodz, University of Perugia, University of Eastern Finland, Kuopio University Hospital, Aristotle University of Thessaloniki, Inserm, Laboratoire Epidémiologie et Analyses en Santé Publique : Risques, Maladies Chroniques et Handicaps, Université de Toulouse, Karolinska Institutet, Stavanger University Hospital, South London and Maudsley NHS Foundation Trust, Warneford Hospital, University of Oxford, University of Würzburg
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,200
Funders: Wellcome Trust, Scottish Government, EU Joint Programme – Neurodegenerative Disease Research, European Federation of Pharmaceutical Industries and Associations, Alzheimer's Society, National Institute for Health and Care Research, British Heart Foundation, Department of Health and Social Care, King's College London, University College London, European Commission, Public Health Agency, Alzheimer’s Research UK, National Institutes of Health, Chief Scientist Office, Scottish Government Health and Social Care Directorate, Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Health and Social Care Research and Development Division, National Institute on Aging, Health Data Research UK
Awards: Identifying DNA methylation signatures in Alzheimer's disease blood, JPND: Targeting epigenetic dysregulation in the brainstem in Alzheimer's Disease (EPI-AD), A multi-faceted approach to epigenomic profiling in Alzheimer's disorder, G200414018, G7185013638, KCL Application for a Mental Health Data Pathfinder award
OpenAlex ID: W3039758274