Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed a...

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Main Authors:	Jia, T., Chu, C., Liu, Y., van Dongen, J., Papastergios, E., Armstrong, Nicola, Bastin, M.E., Carrillo-Roa, T., den Braber, A., Harris, M., Jansen, R., Liu, J., Luciano, M., Ori, A.P.S., Roiz Santiañez, R., Ruggeri, B., Sarkisyan, D., Shin, J., Sungeun, K., Tordesillas Gutiérrez, D., van’t Ent, D., Ames, D., Artiges, E., Bakalkin, G., Banaschewski, T., Bokde, A.L.W., Brodaty, H., Bromberg, U., Brouwer, R., Büchel, C., Burke Quinlan, E., Cahn, W., de Zubicaray, G.I., Ehrlich, S., Ekström, T.J., Flor, H., Fröhner, J.H., Frouin, V., Garavan, H., Gowland, P., Heinz, A., Hoare, J., Ittermann, B., Jahanshad, N., Jiang, J., Kwok, J.B., Martin, N.G., Martinot, J.L., Mather, K.A., McMahon, K.L., McRae, A.F., Nees, F., Papadopoulos Orfanos, D., Paus, T., Poustka, L., Sämann, P.G., Schofield, P.R., Smolka, M.N., Stein, D.J., Strike, L.T., Teeuw, J., Thalamuthu, A., Trollor, J., Walter, H., Wardlaw, J.M., Wen, W., Whelan, R., Apostolova, L.G., Binder, E.B., Boomsma, D.I., Calhoun, V., Crespo-Facorro, B., Deary, I.J., Hulshoff Pol, H., Ophoff, R.A., Pausova, Z., Sachdev, P.S., Saykin, A., Wright, M.J., Thompson, P.M., Schumann, G., Desrivières, S.
Format:	Journal Article
Language:	English
Published:	2021
Online Access:	http://hdl.handle.net/20.500.11937/86965

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author	Jia, T. Chu, C. Liu, Y. van Dongen, J. Papastergios, E. Armstrong, Nicola Bastin, M.E. Carrillo-Roa, T. den Braber, A. Harris, M. Jansen, R. Liu, J. Luciano, M. Ori, A.P.S. Roiz Santiañez, R. Ruggeri, B. Sarkisyan, D. Shin, J. Sungeun, K. Tordesillas Gutiérrez, D. van’t Ent, D. Ames, D. Artiges, E. Bakalkin, G. Banaschewski, T. Bokde, A.L.W. Brodaty, H. Bromberg, U. Brouwer, R. Büchel, C. Burke Quinlan, E. Cahn, W. de Zubicaray, G.I. Ehrlich, S. Ekström, T.J. Flor, H. Fröhner, J.H. Frouin, V. Garavan, H. Gowland, P. Heinz, A. Hoare, J. Ittermann, B. Jahanshad, N. Jiang, J. Kwok, J.B. Martin, N.G. Martinot, J.L. Mather, K.A. McMahon, K.L. McRae, A.F. Nees, F. Papadopoulos Orfanos, D. Paus, T. Poustka, L. Sämann, P.G. Schofield, P.R. Smolka, M.N. Stein, D.J. Strike, L.T. Teeuw, J. Thalamuthu, A. Trollor, J. Walter, H. Wardlaw, J.M. Wen, W. Whelan, R. Apostolova, L.G. Binder, E.B. Boomsma, D.I. Calhoun, V. Crespo-Facorro, B. Deary, I.J. Hulshoff Pol, H. Ophoff, R.A. Pausova, Z. Sachdev, P.S. Saykin, A. Wright, M.J. Thompson, P.M. Schumann, G. Desrivières, S.
author_facet	Jia, T. Chu, C. Liu, Y. van Dongen, J. Papastergios, E. Armstrong, Nicola Bastin, M.E. Carrillo-Roa, T. den Braber, A. Harris, M. Jansen, R. Liu, J. Luciano, M. Ori, A.P.S. Roiz Santiañez, R. Ruggeri, B. Sarkisyan, D. Shin, J. Sungeun, K. Tordesillas Gutiérrez, D. van’t Ent, D. Ames, D. Artiges, E. Bakalkin, G. Banaschewski, T. Bokde, A.L.W. Brodaty, H. Bromberg, U. Brouwer, R. Büchel, C. Burke Quinlan, E. Cahn, W. de Zubicaray, G.I. Ehrlich, S. Ekström, T.J. Flor, H. Fröhner, J.H. Frouin, V. Garavan, H. Gowland, P. Heinz, A. Hoare, J. Ittermann, B. Jahanshad, N. Jiang, J. Kwok, J.B. Martin, N.G. Martinot, J.L. Mather, K.A. McMahon, K.L. McRae, A.F. Nees, F. Papadopoulos Orfanos, D. Paus, T. Poustka, L. Sämann, P.G. Schofield, P.R. Smolka, M.N. Stein, D.J. Strike, L.T. Teeuw, J. Thalamuthu, A. Trollor, J. Walter, H. Wardlaw, J.M. Wen, W. Whelan, R. Apostolova, L.G. Binder, E.B. Boomsma, D.I. Calhoun, V. Crespo-Facorro, B. Deary, I.J. Hulshoff Pol, H. Ophoff, R.A. Pausova, Z. Sachdev, P.S. Saykin, A. Wright, M.J. Thompson, P.M. Schumann, G. Desrivières, S.
author_sort	Jia, T.
building	Curtin Institutional Repository
collection	Online Access
description	DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
first_indexed	2025-11-14T11:26:33Z
format	Journal Article
id	curtin-20.500.11937-86965
institution	Curtin University Malaysia
institution_category	Local University
language	eng
last_indexed	2025-11-14T11:26:33Z
publishDate	2021
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-869652022-01-07T00:33:10Z Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group Jia, T. Chu, C. Liu, Y. van Dongen, J. Papastergios, E. Armstrong, Nicola Bastin, M.E. Carrillo-Roa, T. den Braber, A. Harris, M. Jansen, R. Liu, J. Luciano, M. Ori, A.P.S. Roiz Santiañez, R. Ruggeri, B. Sarkisyan, D. Shin, J. Sungeun, K. Tordesillas Gutiérrez, D. van’t Ent, D. Ames, D. Artiges, E. Bakalkin, G. Banaschewski, T. Bokde, A.L.W. Brodaty, H. Bromberg, U. Brouwer, R. Büchel, C. Burke Quinlan, E. Cahn, W. de Zubicaray, G.I. Ehrlich, S. Ekström, T.J. Flor, H. Fröhner, J.H. Frouin, V. Garavan, H. Gowland, P. Heinz, A. Hoare, J. Ittermann, B. Jahanshad, N. Jiang, J. Kwok, J.B. Martin, N.G. Martinot, J.L. Mather, K.A. McMahon, K.L. McRae, A.F. Nees, F. Papadopoulos Orfanos, D. Paus, T. Poustka, L. Sämann, P.G. Schofield, P.R. Smolka, M.N. Stein, D.J. Strike, L.T. Teeuw, J. Thalamuthu, A. Trollor, J. Walter, H. Wardlaw, J.M. Wen, W. Whelan, R. Apostolova, L.G. Binder, E.B. Boomsma, D.I. Calhoun, V. Crespo-Facorro, B. Deary, I.J. Hulshoff Pol, H. Ophoff, R.A. Pausova, Z. Sachdev, P.S. Saykin, A. Wright, M.J. Thompson, P.M. Schumann, G. Desrivières, S. DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions. 2021 Journal Article http://hdl.handle.net/20.500.11937/86965 10.1038/s41380-019-0605-z eng http://creativecommons.org/licenses/by/4.0/ fulltext
spellingShingle	Jia, T. Chu, C. Liu, Y. van Dongen, J. Papastergios, E. Armstrong, Nicola Bastin, M.E. Carrillo-Roa, T. den Braber, A. Harris, M. Jansen, R. Liu, J. Luciano, M. Ori, A.P.S. Roiz Santiañez, R. Ruggeri, B. Sarkisyan, D. Shin, J. Sungeun, K. Tordesillas Gutiérrez, D. van’t Ent, D. Ames, D. Artiges, E. Bakalkin, G. Banaschewski, T. Bokde, A.L.W. Brodaty, H. Bromberg, U. Brouwer, R. Büchel, C. Burke Quinlan, E. Cahn, W. de Zubicaray, G.I. Ehrlich, S. Ekström, T.J. Flor, H. Fröhner, J.H. Frouin, V. Garavan, H. Gowland, P. Heinz, A. Hoare, J. Ittermann, B. Jahanshad, N. Jiang, J. Kwok, J.B. Martin, N.G. Martinot, J.L. Mather, K.A. McMahon, K.L. McRae, A.F. Nees, F. Papadopoulos Orfanos, D. Paus, T. Poustka, L. Sämann, P.G. Schofield, P.R. Smolka, M.N. Stein, D.J. Strike, L.T. Teeuw, J. Thalamuthu, A. Trollor, J. Walter, H. Wardlaw, J.M. Wen, W. Whelan, R. Apostolova, L.G. Binder, E.B. Boomsma, D.I. Calhoun, V. Crespo-Facorro, B. Deary, I.J. Hulshoff Pol, H. Ophoff, R.A. Pausova, Z. Sachdev, P.S. Saykin, A. Wright, M.J. Thompson, P.M. Schumann, G. Desrivières, S. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
title	Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
title_full	Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
title_fullStr	Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
title_full_unstemmed	Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
title_short	Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
title_sort	epigenome-wide meta-analysis of blood dna methylation and its association with subcortical volumes: findings from the enigma epigenetics working group
url	http://hdl.handle.net/20.500.11937/86965

Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

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