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Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins

As the world's population ages, the age-related cognitive decline presents a great challenge to world's healthcare systems. One of the molecular mechanisms implicated in cognitive ageing is DNA methylation, an epigenetic modification known to be a key player in memory formation, maintenanc...

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Autores principales: Starnawska, Anna, Tan, Qihua, McGue, Matt, Mors, Ole, Børglum, Anders D., Christensen, Kaare, Nyegaard, Mette, Christiansen, Lene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733014/
https://www.ncbi.nlm.nih.gov/pubmed/29311901
http://dx.doi.org/10.3389/fnagi.2017.00413
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author Starnawska, Anna
Tan, Qihua
McGue, Matt
Mors, Ole
Børglum, Anders D.
Christensen, Kaare
Nyegaard, Mette
Christiansen, Lene
author_facet Starnawska, Anna
Tan, Qihua
McGue, Matt
Mors, Ole
Børglum, Anders D.
Christensen, Kaare
Nyegaard, Mette
Christiansen, Lene
author_sort Starnawska, Anna
collection PubMed
description As the world's population ages, the age-related cognitive decline presents a great challenge to world's healthcare systems. One of the molecular mechanisms implicated in cognitive ageing is DNA methylation, an epigenetic modification known to be a key player in memory formation, maintenance, and synaptic plasticity. Using the twin design we performed an epigenome-wide association study (EWAS) in a population of 486 middle-aged monozygotic twins (mean age at follow-up 65.9, SD = 6.1) and correlated their blood DNA methylation to their level (cross-sectional analysis) and change in cognitive abilities over 10 years (longitudinal analysis). We identified several CpG sites where cross-sectional cognitive functioning was associated with DNA methylation levels. The top identified loci were located in ZBTB46 (p = 5.84 × 10(−7)), and TAF12 (p = 4.91 × 10(−7)). KEGG's enrichment analyses of the most associated findings identified “Neuroactive ligand-receptor interaction” as the most enriched pathway (p = 0.0098). Change in cognitive functioning over 10 years was associated with DNA methylation levels in AGBL4 (p = 9.01 × 10(−7)) and SORBS1 (p = 5.28 × 10(−6)), with the first gene playing an important role in neuronal survival and the latter gene implicated before in Alzheimer's disease and ischemic stroke. Our findings point to an association between changes in DNA methylation of genes related to neuronal survival and change of cognitive functioning in aging individuals.
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spelling pubmed-57330142018-01-08 Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins Starnawska, Anna Tan, Qihua McGue, Matt Mors, Ole Børglum, Anders D. Christensen, Kaare Nyegaard, Mette Christiansen, Lene Front Aging Neurosci Neuroscience As the world's population ages, the age-related cognitive decline presents a great challenge to world's healthcare systems. One of the molecular mechanisms implicated in cognitive ageing is DNA methylation, an epigenetic modification known to be a key player in memory formation, maintenance, and synaptic plasticity. Using the twin design we performed an epigenome-wide association study (EWAS) in a population of 486 middle-aged monozygotic twins (mean age at follow-up 65.9, SD = 6.1) and correlated their blood DNA methylation to their level (cross-sectional analysis) and change in cognitive abilities over 10 years (longitudinal analysis). We identified several CpG sites where cross-sectional cognitive functioning was associated with DNA methylation levels. The top identified loci were located in ZBTB46 (p = 5.84 × 10(−7)), and TAF12 (p = 4.91 × 10(−7)). KEGG's enrichment analyses of the most associated findings identified “Neuroactive ligand-receptor interaction” as the most enriched pathway (p = 0.0098). Change in cognitive functioning over 10 years was associated with DNA methylation levels in AGBL4 (p = 9.01 × 10(−7)) and SORBS1 (p = 5.28 × 10(−6)), with the first gene playing an important role in neuronal survival and the latter gene implicated before in Alzheimer's disease and ischemic stroke. Our findings point to an association between changes in DNA methylation of genes related to neuronal survival and change of cognitive functioning in aging individuals. Frontiers Media S.A. 2017-12-12 /pmc/articles/PMC5733014/ /pubmed/29311901 http://dx.doi.org/10.3389/fnagi.2017.00413 Text en Copyright © 2017 Starnawska, Tan, McGue, Mors, Børglum, Christensen, Nyegaard and Christiansen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Starnawska, Anna
Tan, Qihua
McGue, Matt
Mors, Ole
Børglum, Anders D.
Christensen, Kaare
Nyegaard, Mette
Christiansen, Lene
Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins
title Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins
title_full Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins
title_fullStr Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins
title_full_unstemmed Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins
title_short Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins
title_sort epigenome-wide association study of cognitive functioning in middle-aged monozygotic twins
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733014/
https://www.ncbi.nlm.nih.gov/pubmed/29311901
http://dx.doi.org/10.3389/fnagi.2017.00413
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