Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group.
Journal: Molecular psychiatry
Volume: 26
Issue: 8
Year of Publication: 2022
Affiliated Institutions:
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Vrije Universiteit, Amsterdam, Dept Biological Psychology, Van der Boechorststraat , BT, Amsterdam, The Netherlands.
Mathematics and Statistics, Murdoch University, Perth, WA, Australia.
Brain Research Imaging Centre, Centre for Clinical Brain Sciences, and Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh (MEB), Edinburgh, UK.
Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Kraepelinstr, - , Munich, Germany.
Centre for Clinical Brain Sciences and Edinburgh Imaging, University of Edinburgh, Edinburgh, UK.
Department of Psychiatry, VU University Medical Centre, Amsterdam, The Netherlands.
Department of Electrical Engineering, University of New Mexico, Albuquerque, NM, USA.
Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
UCLA Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria, Santander, Spain.
Box , Uppsala biomedicinska centrum BMC, Husarg. , , Uppsala, Sweden.
Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
National Ageing Research Institute, Parkville, VIC, Australia.
Institut National de la Santé et de la Recherche Médicale, INSERM Unit "Neuroimaging & Psychiatry", University Paris Sud-Paris Saclay, University Paris Descartes, Orsay, France.
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J, , Mannheim, Germany.
Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
University Medical Centre Hamburg-Eppendorf, House W, .OG, Martinistr. , , Hamburg, Germany.
Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.
Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Germany.
Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J, Mannheim, Germany.
Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
NeuroSpin, CEA, Université Paris-Saclay, F-, Gif-sur-Yvette, France.
Departments of Psychiatry and Psychology, University of Vermont, , Burlington, VT, USA.
Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.
Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Berlin, Germany.
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA.
Central Clinical School-Brain and Mind Centre, The University of Sydney, Camperdown, NSW, , Australia.
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Herston Imaging Research Facility, School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital and Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, MA E, Canada.
Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str. , , Göttingen, Germany.
Neuroscience Research Australia, Sydney, NSW, Australia.
Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
Brain Research Imaging Centre, Centre for Clinical Brain Sciences, Edinburgh Dementia Research Centre, and Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, , USA.
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. sylvane.desrivieres@kcl.ac.uk.
Abstract summary
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.
Authors & Co-authors:
Jia Tianye T
Chu Congying C
Liu Yun Y
van Dongen Jenny J
Papastergios Evangelos E
Armstrong Nicola J NJ
Bastin Mark E ME
Carrillo-Roa Tania T
den Braber Anouk A
Harris Mathew M
Jansen Rick R
Liu Jingyu J
Luciano Michelle M
Ori Anil P S APS
Roiz Santiañez Roberto R
Ruggeri Barbara B
Sarkisyan Daniil D
Shin Jean J
Sungeun Kim K
Tordesillas Gutiérrez Diana D
Van't Ent Dennis D
Ames David D
Artiges Eric E
Bakalkin Georgy G
Banaschewski Tobias T
Bokde Arun L W ALW
Brodaty Henry H
Bromberg Uli U
Brouwer Rachel R
Büchel Christian C
Burke Quinlan Erin E
Cahn Wiepke W
de Zubicaray Greig I GI
Ehrlich Stefan S
Ekström Tomas J TJ
Flor Herta H
Fröhner Juliane H JH
Frouin Vincent V
Garavan Hugh H
Gowland Penny P
Heinz Andreas A
Hoare Jacqueline J
Ittermann Bernd B
Jahanshad Neda N
Jiang Jiyang J
Kwok John B JB
Martin Nicholas G NG
Martinot Jean-Luc JL
Mather Karen A KA
McMahon Katie L KL
McRae Allan F AF
Nees Frauke F
Papadopoulos Orfanos Dimitri D
Paus Tomáš T
Poustka Luise L
Sämann Philipp G PG
Schofield Peter R PR
Smolka Michael N MN
Stein Dan J DJ
Strike Lachlan T LT
Teeuw Jalmar J
Thalamuthu Anbupalam A
Trollor Julian J
Walter Henrik H
Wardlaw Joanna M JM
Wen Wei W
Whelan Robert R
Apostolova Liana G LG
Binder Elisabeth B EB
Boomsma Dorret I DI
Calhoun Vince V
Crespo-Facorro Benedicto B
Deary Ian J IJ
Hulshoff Pol Hilleke H
Ophoff Roel A RA
Pausova Zdenka Z
Sachdev Perminder S PS
Saykin Andrew A
Wright Margaret J MJ
Thompson Paul M PM
Schumann Gunter G
Desrivières Sylvane S
Study Outcome
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