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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2019Access:
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Jia, T. and Chu, C. and Liu, Y. and van Dongen, J. and Papastergios, E. and Armstrong, N.J. and Bastin, M.E. and Carrillo-Roa, T. and den Braber, A. and Harris, M. and Jansen, R. and Liu, J. and Luciano, M. and Ori, A.P.S. and Roiz Santia??ez, R. and Ruggeri, B. and Sarkisyan, D. and Shin, J. and Sungeun, K. and Tordesillas Guti??rrez, D. and van???t Ent, D. and Ames, D. and Artiges, E. and Bakalkin, G. and Banaschewski, T. and Bokde, A.L.W. and Brodaty, H. and Bromberg, U. and Brouwer, R. and B??chel, C. and Burke Quinlan, E. and Cahn, W. and de Zubicaray, G.I. and Ehrlich, S. and Ekstr??m, T.J. and Flor, H. and Fr??hner, J.H. and Frouin, V. and Garavan, H. and Gowland, P. and Heinz, A. and Hoare, J. and Ittermann, B. and Jahanshad, N. and Jiang, J. and Kwok, J.B. and Martin, N.G. and Martinot, J.-L. and Mather, K.A. and McMahon, K.L. and McRae, A.F. and Nees, F. and Papadopoulos Orfanos, D. and Paus, T. and Poustka, L. and S??mann, P.G. and Schofield, P.R. and Smolka, M.N. and Stein, D.J. and Strike, L.T. and Teeuw, J. and Thalamuthu, A. and Trollor, J. and Walter, H. and Wardlaw, J.M. and Wen, W. and Whelan, R. and Apostolova, L.G. and Binder, E.B. and Boomsma, D.I. and Calhoun, V. and Crespo-Facorro, B. and Deary, I.J. and Hulshoff Pol, H. and Ophoff, R.A. and Pausova, Z. and Sachdev, P.S. and Saykin, A. and Wright, M.J. and Thompson, P.M. and Schumann, G. and Desrivi??res, S., Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group, Molecular Psychiatry, 2019Download Item:
Abstract:
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.
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http://people.tcd.ie/bokdeahttp://people.tcd.ie/whelanr3
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Author: Bokde, Arun; Whelan, Robert
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Molecular PsychiatryAvailability:
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Epigenome-wide meta-analysis of blood DNA methylation, Neurodegeneration, Neuropsychiatric conditionsDOI:
http://dx.doi.org/10.1038/s41380-019-0605-zMetadata
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