Lunnon, Katie and Smith, Rebecca and Hannon, Eilis and De Jager, Philip L and Srivastava, Gyan and Volta, Manuela and Troakes, Claire and Al-Sarraj, Safa and Burrage, Joe and Macdonald, Ruby and Condliffe, Daniel and Harries, Lorna W and Katsel, Pavel and Haroutunian, Vahram and Kaminsky, Zachary and Joachim, Catharine and Powell, John and Lovestone, Simon and Bennett, David A and Schalkwyk, Leonard C and Mill, Jonathan (2014) Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease. Nature Neuroscience, 17 (9). pp. 1164-1170. DOI https://doi.org/10.1038/nn.3782
Lunnon, Katie and Smith, Rebecca and Hannon, Eilis and De Jager, Philip L and Srivastava, Gyan and Volta, Manuela and Troakes, Claire and Al-Sarraj, Safa and Burrage, Joe and Macdonald, Ruby and Condliffe, Daniel and Harries, Lorna W and Katsel, Pavel and Haroutunian, Vahram and Kaminsky, Zachary and Joachim, Catharine and Powell, John and Lovestone, Simon and Bennett, David A and Schalkwyk, Leonard C and Mill, Jonathan (2014) Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease. Nature Neuroscience, 17 (9). pp. 1164-1170. DOI https://doi.org/10.1038/nn.3782
Lunnon, Katie and Smith, Rebecca and Hannon, Eilis and De Jager, Philip L and Srivastava, Gyan and Volta, Manuela and Troakes, Claire and Al-Sarraj, Safa and Burrage, Joe and Macdonald, Ruby and Condliffe, Daniel and Harries, Lorna W and Katsel, Pavel and Haroutunian, Vahram and Kaminsky, Zachary and Joachim, Catharine and Powell, John and Lovestone, Simon and Bennett, David A and Schalkwyk, Leonard C and Mill, Jonathan (2014) Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease. Nature Neuroscience, 17 (9). pp. 1164-1170. DOI https://doi.org/10.1038/nn.3782
Abstract
Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline. We performed a cross-tissue analysis of methylomic variation in AD using samples from four independent human post-mortem brain cohorts. We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from three independent brain cohorts. This study represents, to the best of our knowledge, the first epigenome-wide association study of AD employing a sequential replication design across multiple tissues and highlights the power of this approach for identifying methylomic variation associated with complex disease.
Item Type: | Article |
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Uncontrolled Keywords: | Entorhinal Cortex; Cerebral Cortex; Prefrontal Cortex; Temporal Lobe; Humans; Alzheimer Disease; Ankyrins; DNA Methylation; Epigenesis, Genetic; Aged; Aged, 80 and over; Middle Aged; Female; Male; Genome-Wide Association Study; Transcriptome |
Subjects: | Q Science > QH Natural history > QH426 Genetics |
Divisions: | Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 24 Oct 2014 13:47 |
Last Modified: | 07 Aug 2024 20:36 |
URI: | http://repository.essex.ac.uk/id/eprint/11059 |
Available files
Filename: nihms613258.pdf