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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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2017-12-01
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Series: | Frontiers in Aging Neuroscience |
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Online Access: | http://journal.frontiersin.org/article/10.3389/fnagi.2017.00413/full |
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doaj-aa241481855c417b9e55fa9667fa66db |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Starnawska Anna Starnawska Anna Starnawska Qihua Tan Qihua Tan Matt McGue Matt McGue Ole Mors Ole Mors Ole Mors Anders D. Børglum Anders D. Børglum Anders D. Børglum Kaare Christensen Kaare Christensen Kaare Christensen Kaare Christensen Mette Nyegaard Mette Nyegaard Mette Nyegaard Lene Christiansen Lene Christiansen |
spellingShingle |
Anna Starnawska Anna Starnawska Anna Starnawska Qihua Tan Qihua Tan Matt McGue Matt McGue Ole Mors Ole Mors Ole Mors Anders D. Børglum Anders D. Børglum Anders D. Børglum Kaare Christensen Kaare Christensen Kaare Christensen Kaare Christensen Mette Nyegaard Mette Nyegaard Mette Nyegaard Lene Christiansen Lene Christiansen Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins Frontiers in Aging Neuroscience epigenome-wide association study DNA methylation epigenetic epidemiology cognition cognitive aging whole blood |
author_facet |
Anna Starnawska Anna Starnawska Anna Starnawska Qihua Tan Qihua Tan Matt McGue Matt McGue Ole Mors Ole Mors Ole Mors Anders D. Børglum Anders D. Børglum Anders D. Børglum Kaare Christensen Kaare Christensen Kaare Christensen Kaare Christensen Mette Nyegaard Mette Nyegaard Mette Nyegaard Lene Christiansen Lene Christiansen |
author_sort |
Anna Starnawska |
title |
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_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_sort |
epigenome-wide association study of cognitive functioning in middle-aged monozygotic twins |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Aging Neuroscience |
issn |
1663-4365 |
publishDate |
2017-12-01 |
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. |
topic |
epigenome-wide association study DNA methylation epigenetic epidemiology cognition cognitive aging whole blood |
url |
http://journal.frontiersin.org/article/10.3389/fnagi.2017.00413/full |
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doaj-aa241481855c417b9e55fa9667fa66db2020-11-24T22:56:57ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652017-12-01910.3389/fnagi.2017.00413304820Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic TwinsAnna Starnawska0Anna Starnawska1Anna Starnawska2Qihua Tan3Qihua Tan4Matt McGue5Matt McGue6Ole Mors7Ole Mors8Ole Mors9Anders D. Børglum10Anders D. Børglum11Anders D. Børglum12Kaare Christensen13Kaare Christensen14Kaare Christensen15Kaare Christensen16Mette Nyegaard17Mette Nyegaard18Mette Nyegaard19Lene Christiansen20Lene Christiansen21The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkCenter for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, DenmarkThe Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, DenmarkDepartment of Clinical Genetics, Odense University Hospital, Odense, DenmarkThe Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, DenmarkDepartment of Psychology, University of Minnesota, Minneapolis, MN, United StatesThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, DenmarkCenter for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, DenmarkPsychosis Research Unit, Aarhus University Hospital, Risskov, DenmarkThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkCenter for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, DenmarkThe Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, DenmarkDepartment of Clinical Genetics, Odense University Hospital, Odense, DenmarkThe Danish Aging Research Center, Institute of Public Health, University of Southern Denmark, Odense, DenmarkDepartment of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, DenmarkThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkCenter for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, DenmarkThe Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, DenmarkThe Danish Aging Research Center, Institute of Public Health, University of Southern Denmark, Odense, DenmarkAs 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.http://journal.frontiersin.org/article/10.3389/fnagi.2017.00413/fullepigenome-wide association studyDNA methylationepigenetic epidemiologycognitioncognitive agingwhole blood |