Meta-analysis of epigenome-wide association studies of cognitive abilities.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620679
Title:
Meta-analysis of epigenome-wide association studies of cognitive abilities.
Authors:
Marioni, R, E. [et al]; Mill, Jonathan
Abstract:
Cognitive functions are important correlates of health outcomes across the life-course. Individual differences in cognitive functions are partly heritable. Epigenetic modifications, such as DNA methylation, are susceptible to both genetic and environmental factors and may provide insights into individual differences in cognitive functions. Epigenome-wide meta-analyses for blood-based DNA methylation levels at ~420,000 CpG sites were performed for seven measures of cognitive functioning using data from 11 cohorts. CpGs that passed a Bonferroni correction, adjusting for the number of CpGs and cognitive tests, were assessed for: longitudinal change; being under genetic control (methylation QTLs); and associations with brain health (structural MRI), brain methylation and Alzheimer's disease pathology. Across the seven measures of cognitive functioning (meta-analysis n range: 2557-6809), there were epigenome-wide significant (P < 1.7 × 10-8) associations for global cognitive function (cg21450381, P = 1.6 × 10-8), and phonemic verbal fluency (cg12507869, P = 2.5 × 10-9). The CpGs are located in an intergenic region on chromosome 12 and the INPP5A gene on chromosome 10, respectively. Both probes have moderate correlations (~0.4) with brain methylation in Brodmann area 20 (ventral temporal cortex). Neither probe showed evidence of longitudinal change in late-life or associations with white matter brain MRI measures in one cohort with these data. A methylation QTL analysis suggested that rs113565688 was a cis methylation QTL for cg12507869 (P = 5 × 10-5 and 4 × 10-13 in two lookup cohorts). We demonstrate a link between blood-based DNA methylation and measures of phonemic verbal fluency and global cognitive ability. Further research is warranted to understand the mechanisms linking genomic regulatory changes with cognitive function to health and disease.
Citation:
Meta-analysis of epigenome-wide association studies of cognitive abilities. 2018 Mol. Psychiatry
Publisher:
Nature
Journal:
Molecular psychiatry
Issue Date:
8-Jan-2018
URI:
http://hdl.handle.net/11287/620679
DOI:
10.1038/s41380-017-0008-y
PubMed ID:
29311653
Additional Links:
http://dx.doi.org/10.1038/s41380-017-0008-y
Type:
Journal Article
Language:
en
ISSN:
1476-5578
Appears in Collections:
Honorary contracts publications; 2018 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorMarioni, R, E. [et al]en
dc.contributor.authorMill, Jonathanen
dc.date.accessioned2018-05-08T08:39:20Z-
dc.date.available2018-05-08T08:39:20Z-
dc.date.issued2018-01-08-
dc.identifier.citationMeta-analysis of epigenome-wide association studies of cognitive abilities. 2018 Mol. Psychiatryen
dc.identifier.issn1476-5578-
dc.identifier.pmid29311653-
dc.identifier.doi10.1038/s41380-017-0008-y-
dc.identifier.urihttp://hdl.handle.net/11287/620679-
dc.description.abstractCognitive functions are important correlates of health outcomes across the life-course. Individual differences in cognitive functions are partly heritable. Epigenetic modifications, such as DNA methylation, are susceptible to both genetic and environmental factors and may provide insights into individual differences in cognitive functions. Epigenome-wide meta-analyses for blood-based DNA methylation levels at ~420,000 CpG sites were performed for seven measures of cognitive functioning using data from 11 cohorts. CpGs that passed a Bonferroni correction, adjusting for the number of CpGs and cognitive tests, were assessed for: longitudinal change; being under genetic control (methylation QTLs); and associations with brain health (structural MRI), brain methylation and Alzheimer's disease pathology. Across the seven measures of cognitive functioning (meta-analysis n range: 2557-6809), there were epigenome-wide significant (P < 1.7 × 10-8) associations for global cognitive function (cg21450381, P = 1.6 × 10-8), and phonemic verbal fluency (cg12507869, P = 2.5 × 10-9). The CpGs are located in an intergenic region on chromosome 12 and the INPP5A gene on chromosome 10, respectively. Both probes have moderate correlations (~0.4) with brain methylation in Brodmann area 20 (ventral temporal cortex). Neither probe showed evidence of longitudinal change in late-life or associations with white matter brain MRI measures in one cohort with these data. A methylation QTL analysis suggested that rs113565688 was a cis methylation QTL for cg12507869 (P = 5 × 10-5 and 4 × 10-13 in two lookup cohorts). We demonstrate a link between blood-based DNA methylation and measures of phonemic verbal fluency and global cognitive ability. Further research is warranted to understand the mechanisms linking genomic regulatory changes with cognitive function to health and disease.en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://dx.doi.org/10.1038/s41380-017-0008-yen
dc.rightsArchived with thanks to Molecular psychiatryen
dc.subjectWessex Classification Subject Headings::Psychologyen
dc.titleMeta-analysis of epigenome-wide association studies of cognitive abilities.en
dc.typeJournal Articleen
dc.identifier.journalMolecular psychiatryen
dc.type.versionIn press (epub ahead of print)en

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