Epigenome-wide association study of cognitive functioning in middle-aged monozygotic twins

Anna Starnawska*, Qihua Tan, Matt McGue, Ole Mors, Anders D. Børglum, Kaare Christensen, Mette Nyegaard, Lene Christiansen

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article number413
JournalFrontiers in Aging Neuroscience
Volume9
Issue numberDEC
Number of pages10
ISSN1663-4365
DOIs
Publication statusPublished - 2017

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Monozygotic Twins
DNA Methylation
Epigenomics
Population
Alzheimer Disease
Cross-Sectional Studies
Maintenance
Ligands
Delivery of Health Care

Keywords

  • Cognition
  • Cognitive aging
  • DNA methylation
  • Epigenetic epidemiology
  • Epigenome-wide association study
  • Monozygotic twins
  • Whole blood

Cite this

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title = "Epigenome-wide association study of cognitive functioning in middle-aged monozygotic twins",
abstract = "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.",
keywords = "Cognition, Cognitive aging, DNA methylation, Epigenetic epidemiology, Epigenome-wide association study, Monozygotic twins, Whole blood",
author = "Anna Starnawska and Qihua Tan and Matt McGue and Ole Mors and B{\o}rglum, {Anders D.} and Kaare Christensen and Mette Nyegaard and Lene Christiansen",
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journal = "Frontiers in Aging Neuroscience",
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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.

In: Frontiers in Aging Neuroscience, Vol. 9, No. DEC, 413, 2017.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Epigenome-wide association study of cognitive functioning in middle-aged monozygotic twins

AU - Starnawska, Anna

AU - Tan, Qihua

AU - McGue, Matt

AU - Mors, Ole

AU - Børglum, Anders D.

AU - Christensen, Kaare

AU - Nyegaard, Mette

AU - Christiansen, Lene

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Cognition

KW - Cognitive aging

KW - DNA methylation

KW - Epigenetic epidemiology

KW - Epigenome-wide association study

KW - Monozygotic twins

KW - Whole blood

U2 - 10.3389/fnagi.2017.00413

DO - 10.3389/fnagi.2017.00413

M3 - Journal article

C2 - 29311901

AN - SCOPUS:85038001649

VL - 9

JO - Frontiers in Aging Neuroscience

JF - Frontiers in Aging Neuroscience

SN - 1663-4365

IS - DEC

M1 - 413

ER -