Elevated DNA methylation across a 48‐kb region spanning the HOXA gene cluster is associated with Alzheimer's disease neuropathology
Year: 2018
Type: article
Study design: Observational Study
Abstract: Introduction Alzheimer's disease is a neurodegenerative disorder that is hypothesized to involve epigenetic dysregulation of gene expression in the brain. Methods We performed an epigenome‐wide association study to identify differential DNA methylation associated with neuropathology in prefrontal cortex and superior temporal gyrus samples from 147 individuals, replicating our findings in two independent data sets (N = 117 and 740). Results We identify elevated DNA methylation associated with neuropathology across a 48‐kb region spanning 208 CpG sites within the HOXA gene cluster. A meta‐analysis of the top‐ranked probe within the HOXA3 gene (cg22962123) highlighted significant hypermethylation across all three cohorts (P = 3.11 × 10−18). Discussion We present robust evidence for elevated DNA methylation associated with Alzheimer's disease neuropathology spanning the HOXA gene cluster on chromosome 7. These data add to the growing evidence highlighting a role for epigenetic variation in Alzheimer's disease, implicating the HOX gene family as a target for future investigation.
Source: Alzheimer s & Dementia
Institutions: University of Exeter, Royal Devon and Exeter Hospital, Exeter Hospital, Brigham and Women's Hospital, Harvard University, Columbia University Irving Medical Center, Columbia University, King's College London, Queen Mary University of London, James J. Peters VA Medical Center, Icahn School of Medicine at Mount Sinai, Rush University Medical Center, Warneford Hospital, University of Oxford, University of Essex
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Estimated APC paid: $3,528
Funders: U.S. Department of Veterans Affairs, Alzheimer's Association, BRACE, Alzheimer's Society, National Institutes of Health, Medical Research Council, National Institute on Aging, National Institute of Mental Health, National Institute of Environmental Health Sciences, National Center for Research Resources
Awards: Integrative analysis of genomic and epigenomic architecture in cognitive decline, G1751565318, A multi-faceted approach to epigenomic profiling in Alzheimer's disorder, G200414018, G2830398374, Plasma AB as a Surrogate Genetic Marker for LOAD, Exploring the Role of the Brain Transcriptome in Cognitive Decline, G3159755494, Alzheimer's Disease Research Center, G3743240706, The role of 5-hydroxymethylation in Alzheimer’s disease brain, Mayo Clinic Center for Translational Science Activities, G4005715684, G413369726, G4607554797, Exploring the Role of the Brain Epigenome: Cognitive Decline and Life Experiences, G4970245363, G5864276340, Contribution of cell cycle processes to myelin deficits in schizophrenia, G6119153054, G6570194216, G6871612717, Genome wide association study of gene expression levels in Alzheimer's disease, G828200374, Clinical and Biological Studies of Early AD, Exploring the Role of the Brain Epigenome: Cognitive Decline and Life Experiences, G9000005508, G9000011116, G9000015626, G9000020322, G9000099765, G9000152567, G9000173373, G9000244657, G9000247718, G9000281821, G9000285961, G9000332693, G983864884
OpenAlex ID: W2789414284