Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease
Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive neuropathology and cognitive decline. Here the authors describe an epigenome-wide association study (EWAS) of human post-mortem brain samples across multiple independent AD cohorts. They find consisten...
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| Veröffentlicht in: | Nature neuroscience 2014-09, Vol.17 (9), p.1164-1170 |
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| creator | Lunnon, Katie Smith, Rebecca Hannon, Eilis De Jager, Philip L Srivastava, Gyan Volta, Manuela Troakes, Claire Al-Sarraj, Safa Burrage, Joe Macdonald, Ruby Condliffe, Daniel Harries, Lorna W Katsel, Pavel Haroutunian, Vahram Kaminsky, Zachary Joachim, Catharine Powell, John Lovestone, Simon Bennett, David A Schalkwyk, Leonard C Mill, Jonathan |
| description | Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive neuropathology and cognitive decline. Here the authors describe an epigenome-wide association study (EWAS) of human post-mortem brain samples across multiple independent AD cohorts. They find consistent hypermethylation of the
ANK1
gene associated with neuropathology.
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. |
| doi_str_mv | 10.1038/nn.3782 |
| format | Article |
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ANK1
gene associated with neuropathology.
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.</description><identifier>ISSN: 1097-6256</identifier><identifier>EISSN: 1546-1726</identifier><identifier>DOI: 10.1038/nn.3782</identifier><identifier>PMID: 25129077</identifier><identifier>CODEN: NANEFN</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>45 ; 45/22 ; 45/61 ; 45/77 ; 631/1647/2210/2213 ; 631/208/177 ; 631/378/1689/1283 ; Aged ; Aged, 80 and over ; Alzheimer Disease - epidemiology ; Alzheimer Disease - genetics ; Alzheimer Disease - pathology ; Alzheimer's disease ; Animal Genetics and Genomics ; Ankyrins - genetics ; Behavioral Sciences ; Biological Techniques ; Biomedicine ; Brain ; Cerebellum ; Cerebral Cortex - pathology ; Cerebral Cortex - physiology ; Development and progression ; DNA methylation ; DNA Methylation - genetics ; Entorhinal cortex ; Entorhinal Cortex - pathology ; Entorhinal Cortex - physiology ; Epigenesis, Genetic - genetics ; Epigenetics ; Female ; Genetic aspects ; Genome-Wide Association Study ; Hospitals ; Humans ; Male ; Methylation ; Middle Aged ; Neurobiology ; Neurodegeneration ; Neuropathology ; Neurosciences ; Patient outcomes ; Prefrontal Cortex - pathology ; Prefrontal Cortex - physiology ; Psychiatry ; Risk factors ; Temporal Lobe - pathology ; Temporal Lobe - physiology ; Transcriptome</subject><ispartof>Nature neuroscience, 2014-09, Vol.17 (9), p.1164-1170</ispartof><rights>Springer Nature America, Inc. 2014</rights><rights>COPYRIGHT 2014 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c683t-effc0edebcdd247aba89679e174268487db33284adde775a21d94752f633571b3</citedby><cites>FETCH-LOGICAL-c683t-effc0edebcdd247aba89679e174268487db33284adde775a21d94752f633571b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nn.3782$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nn.3782$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25129077$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lunnon, Katie</creatorcontrib><creatorcontrib>Smith, Rebecca</creatorcontrib><creatorcontrib>Hannon, Eilis</creatorcontrib><creatorcontrib>De Jager, Philip L</creatorcontrib><creatorcontrib>Srivastava, Gyan</creatorcontrib><creatorcontrib>Volta, Manuela</creatorcontrib><creatorcontrib>Troakes, Claire</creatorcontrib><creatorcontrib>Al-Sarraj, Safa</creatorcontrib><creatorcontrib>Burrage, Joe</creatorcontrib><creatorcontrib>Macdonald, Ruby</creatorcontrib><creatorcontrib>Condliffe, Daniel</creatorcontrib><creatorcontrib>Harries, Lorna W</creatorcontrib><creatorcontrib>Katsel, Pavel</creatorcontrib><creatorcontrib>Haroutunian, Vahram</creatorcontrib><creatorcontrib>Kaminsky, Zachary</creatorcontrib><creatorcontrib>Joachim, Catharine</creatorcontrib><creatorcontrib>Powell, John</creatorcontrib><creatorcontrib>Lovestone, Simon</creatorcontrib><creatorcontrib>Bennett, David A</creatorcontrib><creatorcontrib>Schalkwyk, Leonard C</creatorcontrib><creatorcontrib>Mill, Jonathan</creatorcontrib><title>Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease</title><title>Nature neuroscience</title><addtitle>Nat Neurosci</addtitle><addtitle>Nat Neurosci</addtitle><description>Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive neuropathology and cognitive decline. Here the authors describe an epigenome-wide association study (EWAS) of human post-mortem brain samples across multiple independent AD cohorts. They find consistent hypermethylation of the
ANK1
gene associated with neuropathology.
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.</description><subject>45</subject><subject>45/22</subject><subject>45/61</subject><subject>45/77</subject><subject>631/1647/2210/2213</subject><subject>631/208/177</subject><subject>631/378/1689/1283</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - epidemiology</subject><subject>Alzheimer Disease - genetics</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer's disease</subject><subject>Animal Genetics and Genomics</subject><subject>Ankyrins - genetics</subject><subject>Behavioral Sciences</subject><subject>Biological Techniques</subject><subject>Biomedicine</subject><subject>Brain</subject><subject>Cerebellum</subject><subject>Cerebral Cortex - pathology</subject><subject>Cerebral Cortex - physiology</subject><subject>Development and progression</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>Entorhinal cortex</subject><subject>Entorhinal Cortex - pathology</subject><subject>Entorhinal Cortex - physiology</subject><subject>Epigenesis, Genetic - genetics</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genome-Wide Association Study</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Male</subject><subject>Methylation</subject><subject>Middle Aged</subject><subject>Neurobiology</subject><subject>Neurodegeneration</subject><subject>Neuropathology</subject><subject>Neurosciences</subject><subject>Patient outcomes</subject><subject>Prefrontal Cortex - pathology</subject><subject>Prefrontal Cortex - physiology</subject><subject>Psychiatry</subject><subject>Risk factors</subject><subject>Temporal Lobe - pathology</subject><subject>Temporal Lobe - 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epidemiology</topic><topic>Alzheimer Disease - genetics</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer's disease</topic><topic>Animal Genetics and Genomics</topic><topic>Ankyrins - genetics</topic><topic>Behavioral Sciences</topic><topic>Biological Techniques</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Cerebellum</topic><topic>Cerebral Cortex - pathology</topic><topic>Cerebral Cortex - physiology</topic><topic>Development and progression</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>Entorhinal cortex</topic><topic>Entorhinal Cortex - pathology</topic><topic>Entorhinal Cortex - physiology</topic><topic>Epigenesis, Genetic - genetics</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Genome-Wide Association Study</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Male</topic><topic>Methylation</topic><topic>Middle Aged</topic><topic>Neurobiology</topic><topic>Neurodegeneration</topic><topic>Neuropathology</topic><topic>Neurosciences</topic><topic>Patient outcomes</topic><topic>Prefrontal Cortex - 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Academic</collection><jtitle>Nature neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lunnon, Katie</au><au>Smith, Rebecca</au><au>Hannon, Eilis</au><au>De Jager, Philip L</au><au>Srivastava, Gyan</au><au>Volta, Manuela</au><au>Troakes, Claire</au><au>Al-Sarraj, Safa</au><au>Burrage, Joe</au><au>Macdonald, Ruby</au><au>Condliffe, Daniel</au><au>Harries, Lorna W</au><au>Katsel, Pavel</au><au>Haroutunian, Vahram</au><au>Kaminsky, Zachary</au><au>Joachim, Catharine</au><au>Powell, John</au><au>Lovestone, Simon</au><au>Bennett, David A</au><au>Schalkwyk, Leonard C</au><au>Mill, Jonathan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease</atitle><jtitle>Nature neuroscience</jtitle><stitle>Nat Neurosci</stitle><addtitle>Nat Neurosci</addtitle><date>2014-09-01</date><risdate>2014</risdate><volume>17</volume><issue>9</issue><spage>1164</spage><epage>1170</epage><pages>1164-1170</pages><issn>1097-6256</issn><eissn>1546-1726</eissn><coden>NANEFN</coden><abstract>Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive neuropathology and cognitive decline. Here the authors describe an epigenome-wide association study (EWAS) of human post-mortem brain samples across multiple independent AD cohorts. They find consistent hypermethylation of the
ANK1
gene associated with neuropathology.
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.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>25129077</pmid><doi>10.1038/nn.3782</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1097-6256 |
| ispartof | Nature neuroscience, 2014-09, Vol.17 (9), p.1164-1170 |
| issn | 1097-6256 1546-1726 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1664194600 |
| source | MEDLINE; SpringerLink Journals; Nature |
| subjects | 45 45/22 45/61 45/77 631/1647/2210/2213 631/208/177 631/378/1689/1283 Aged Aged, 80 and over Alzheimer Disease - epidemiology Alzheimer Disease - genetics Alzheimer Disease - pathology Alzheimer's disease Animal Genetics and Genomics Ankyrins - genetics Behavioral Sciences Biological Techniques Biomedicine Brain Cerebellum Cerebral Cortex - pathology Cerebral Cortex - physiology Development and progression DNA methylation DNA Methylation - genetics Entorhinal cortex Entorhinal Cortex - pathology Entorhinal Cortex - physiology Epigenesis, Genetic - genetics Epigenetics Female Genetic aspects Genome-Wide Association Study Hospitals Humans Male Methylation Middle Aged Neurobiology Neurodegeneration Neuropathology Neurosciences Patient outcomes Prefrontal Cortex - pathology Prefrontal Cortex - physiology Psychiatry Risk factors Temporal Lobe - pathology Temporal Lobe - physiology Transcriptome |
| title | Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T02%3A22%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Methylomic%20profiling%20implicates%20cortical%20deregulation%20of%20ANK1%20in%20Alzheimer's%20disease&rft.jtitle=Nature%20neuroscience&rft.au=Lunnon,%20Katie&rft.date=2014-09-01&rft.volume=17&rft.issue=9&rft.spage=1164&rft.epage=1170&rft.pages=1164-1170&rft.issn=1097-6256&rft.eissn=1546-1726&rft.coden=NANEFN&rft_id=info:doi/10.1038/nn.3782&rft_dat=%3Cgale_proqu%3EA382150454%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1656322780&rft_id=info:pmid/25129077&rft_galeid=A382150454&rfr_iscdi=true |