TY - JOUR
T1 - An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene
AU - Roubroeks, Janou A.Y.
AU - Smith, Adam R.
AU - Smith, Rebecca G.
AU - Pishva, Ehsan
AU - Ibrahim, Zina
AU - Sattlecker, Martina
AU - Hannon, Eilis J.
AU - Kłoszewska, Iwona
AU - Mecocci, Patrizia
AU - Soininen, Hilkka
AU - Tsolaki, Magda
AU - Vellas, Bruno
AU - Wahlund, Lars Olof
AU - Aarsland, Dag
AU - Proitsi, Petroula
AU - Hodges, Angela
AU - Lovestone, Simon
AU - Newhouse, Stephen J.
AU - Dobson, Richard J.B.
AU - Mill, Jonathan
AU - van den Hove, Daniël L.A.
AU - Lunnon, Katie
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Alzheimer's disease (AD)
KW - Biomarker
KW - Blood
KW - DNA methylation
KW - HOXB6
KW - Mild cognitive impairment (MCI)
UR - http://www.scopus.com/inward/record.url?scp=85088797676&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2020.06.023
DO - 10.1016/j.neurobiolaging.2020.06.023
M3 - Article
AN - SCOPUS:85088797676
SN - 0197-4580
VL - 95
SP - 26
EP - 45
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -