Imprinting methylation predicts hippocampal volumes and hyperintensities and the change with age in later life

Abstract Epigenetic imprinting is important for neurogenesis and brain function. Hippocampal volumes and brain hyperintensities in late life have been associated with early life circumstances. Epigenetic imprinting may underpin these associations. Methylation was measured at 982 sites in 13 imprinte...

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Autores principales: Marlene Lorgen-Ritchie, Alison D. Murray, Roger Staff, Anne C. Ferguson-Smith, Marcus Richards, Graham W. Horgan, Louise H. Phillips, Gwen Hoad, Chris McNeil, Antonio Ribeiro, Paul Haggarty
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:40a080c1acde4c3bb914d447e8eb98772021-12-02T14:01:22ZImprinting methylation predicts hippocampal volumes and hyperintensities and the change with age in later life10.1038/s41598-020-78062-22045-2322https://doaj.org/article/40a080c1acde4c3bb914d447e8eb98772021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78062-2https://doaj.org/toc/2045-2322Abstract Epigenetic imprinting is important for neurogenesis and brain function. Hippocampal volumes and brain hyperintensities in late life have been associated with early life circumstances. Epigenetic imprinting may underpin these associations. Methylation was measured at 982 sites in 13 imprinted locations in blood samples from a longitudinal cohort by bisulphite amplicon sequencing. Hippocampal volumes and hyperintensities were determined at age 64y and 72y using MRI. Hyperintensities were determined in white matter, grey matter and infratentorial regions. Permutation methods were used to adjust for multiple testing. At 64y, H19/IGF2 and NESPAS methylation predicted hippocampal volumes. PEG3 predicted hyperintensities in hippocampal grey matter, and white matter. GNASXL predicted grey matter hyperintensities. Changes with age were predicted for hippocampal volume (MEST1, KvDMR, L3MBTL, GNASXL), white matter (MEST1, PEG3) and hippocampal grey matter hyperintensities (MCTS2, GNASXL, NESPAS, L3MBTL, MCTS2, SNRPN, MEST1). Including childhood cognitive ability, years in education, or socioeconomic status as additional explanatory variables in regression analyses did not change the overall findings. Imprinting methylation in multiple genes predicts brain structures, and their change over time. These findings are potentially relevant to the development of novel tests of brain structure and function across the life-course, strategies to improve cognitive outcomes, and our understanding of early influences on brain development and function.Marlene Lorgen-RitchieAlison D. MurrayRoger StaffAnne C. Ferguson-SmithMarcus RichardsGraham W. HorganLouise H. PhillipsGwen HoadChris McNeilAntonio RibeiroPaul HaggartyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Marlene Lorgen-Ritchie
Alison D. Murray
Roger Staff
Anne C. Ferguson-Smith
Marcus Richards
Graham W. Horgan
Louise H. Phillips
Gwen Hoad
Chris McNeil
Antonio Ribeiro
Paul Haggarty
Imprinting methylation predicts hippocampal volumes and hyperintensities and the change with age in later life
description Abstract Epigenetic imprinting is important for neurogenesis and brain function. Hippocampal volumes and brain hyperintensities in late life have been associated with early life circumstances. Epigenetic imprinting may underpin these associations. Methylation was measured at 982 sites in 13 imprinted locations in blood samples from a longitudinal cohort by bisulphite amplicon sequencing. Hippocampal volumes and hyperintensities were determined at age 64y and 72y using MRI. Hyperintensities were determined in white matter, grey matter and infratentorial regions. Permutation methods were used to adjust for multiple testing. At 64y, H19/IGF2 and NESPAS methylation predicted hippocampal volumes. PEG3 predicted hyperintensities in hippocampal grey matter, and white matter. GNASXL predicted grey matter hyperintensities. Changes with age were predicted for hippocampal volume (MEST1, KvDMR, L3MBTL, GNASXL), white matter (MEST1, PEG3) and hippocampal grey matter hyperintensities (MCTS2, GNASXL, NESPAS, L3MBTL, MCTS2, SNRPN, MEST1). Including childhood cognitive ability, years in education, or socioeconomic status as additional explanatory variables in regression analyses did not change the overall findings. Imprinting methylation in multiple genes predicts brain structures, and their change over time. These findings are potentially relevant to the development of novel tests of brain structure and function across the life-course, strategies to improve cognitive outcomes, and our understanding of early influences on brain development and function.
format article
author Marlene Lorgen-Ritchie
Alison D. Murray
Roger Staff
Anne C. Ferguson-Smith
Marcus Richards
Graham W. Horgan
Louise H. Phillips
Gwen Hoad
Chris McNeil
Antonio Ribeiro
Paul Haggarty
author_facet Marlene Lorgen-Ritchie
Alison D. Murray
Roger Staff
Anne C. Ferguson-Smith
Marcus Richards
Graham W. Horgan
Louise H. Phillips
Gwen Hoad
Chris McNeil
Antonio Ribeiro
Paul Haggarty
author_sort Marlene Lorgen-Ritchie
title Imprinting methylation predicts hippocampal volumes and hyperintensities and the change with age in later life
title_short Imprinting methylation predicts hippocampal volumes and hyperintensities and the change with age in later life
title_full Imprinting methylation predicts hippocampal volumes and hyperintensities and the change with age in later life
title_fullStr Imprinting methylation predicts hippocampal volumes and hyperintensities and the change with age in later life
title_full_unstemmed Imprinting methylation predicts hippocampal volumes and hyperintensities and the change with age in later life
title_sort imprinting methylation predicts hippocampal volumes and hyperintensities and the change with age in later life
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/40a080c1acde4c3bb914d447e8eb9877
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