Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
31811260
TITLE
Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group.
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.
DATE PUBLISHED
2019 Dec 06
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2019/03/30
accepted 2019/11/12
revised 2019/11/09
entrez 2019/12/08 06:00
pubmed 2019/12/08 06:00
medline 2019/12/08 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Jia T Jia Tianye T MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China.
Chu C Chu Congying C Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Liu Y Liu Yun Y 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.
van Dongen J van Dongen Jenny J Vrije Universiteit, Amsterdam, Dept Biological Psychology, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
Papastergios E Papastergios Evangelos E Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Armstrong NJ Armstrong Nicola J NJ Mathematics and Statistics, Murdoch University, Perth, WA, Australia.
Bastin ME Bastin Mark E ME Brain Research Imaging Centre, Centre for Clinical Brain Sciences, and Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh (MEB), Edinburgh, UK.
Carrillo-Roa T Carrillo-Roa Tania T Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Kraepelinstr, 2-10 80804, Munich, Germany.
den Braber A den Braber Anouk A Vrije Universiteit, Amsterdam, Dept Biological Psychology, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
Harris M Harris Mathew M Centre for Clinical Brain Sciences and Edinburgh Imaging, University of Edinburgh, Edinburgh, UK.
Jansen R Jansen Rick R Department of Psychiatry, VU University Medical Centre, Amsterdam, The Netherlands.
Liu J Liu Jingyu J Department of Electrical Engineering, University of New Mexico, Albuquerque, NM, USA.
Luciano M Luciano Michelle M Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Ori APS Ori Anil P S APS UCLA Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Roiz Santiañez R Roiz Santiañez Roberto R Centro Investigación Biomédica en Red de Salud Mental, Santander, Spain.
Ruggeri B Ruggeri Barbara B Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Sarkisyan D Sarkisyan Daniil D Box 591, Uppsala biomedicinska centrum BMC, Husarg. 3, 751 24, Uppsala, Sweden.
Shin J Shin Jean J Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Sungeun K Sungeun Kim K Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
Tordesillas Gutiérrez D Tordesillas Gutiérrez Diana D Neuroimaging Unit, Technological Facilities. Valdecilla Biomedical Research Institute IDIVAL, Santander, Cantabria, Spain.
Van't Ent D Van't Ent Dennis D Vrije Universiteit, Amsterdam, Dept Biological Psychology, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
Ames D Ames David D Academic Unit for Psychiatry of Old Age, University of Melbourne, St George's Hospital, Kew, VIC, Australia.
Artiges E Artiges Eric E GH Nord Essonne Psychiatry Department 91G16, Orsay, France.
Bakalkin G Bakalkin Georgy G Box 591, Uppsala biomedicinska centrum BMC, Husarg. 3, 751 24, Uppsala, Sweden.
Banaschewski T Banaschewski Tobias T Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159, Mannheim, Germany.
Bokde ALW Bokde Arun L W ALW Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Brodaty H Brodaty Henry H Dementia Centre for Research Collaboration, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Bromberg U Bromberg Uli U University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, 20246, Hamburg, Germany.
Brouwer R Brouwer Rachel R Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Büchel C Büchel Christian C University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, 20246, Hamburg, Germany.
Burke Quinlan E Burke Quinlan Erin E Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Cahn W Cahn Wiepke W Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
de Zubicaray GI de Zubicaray Greig I GI Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.
Ehrlich S Ehrlich Stefan S Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Germany.
Ekström TJ Ekström Tomas J TJ Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Flor H Flor Herta H Department of Psychology, School of Social Sciences, University of Mannheim, 68131, Mannheim, Germany.
Fröhner JH Fröhner Juliane H JH Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
Frouin V Frouin Vincent V NeuroSpin, CEA, Université Paris-Saclay, F-91191, Gif-sur-Yvette, France.
Garavan H Garavan Hugh H Departments of Psychiatry and Psychology, University of Vermont, 05405, Burlington, VT, USA.
Gowland P Gowland Penny P Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.
Heinz A Heinz Andreas A Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charitéplatz 1, Berlin, Germany.
Hoare J Hoare Jacqueline J Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Ittermann B Ittermann Bernd B Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Berlin, Germany.
Jahanshad N Jahanshad Neda N 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.
Jiang J Jiang Jiyang J Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Kwok JB Kwok John B JB School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Martin NG Martin Nicholas G NG Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Martinot JL Martinot Jean-Luc JL Maison de Solenn, Cochin Hospital, Paris, France.
Mather KA Mather Karen A KA Neuroscience Research Australia, Sydney, NSW, Australia.
McMahon KL McMahon Katie L KL Herston Imaging Research Facility, School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
McRae AF McRae Allan F AF Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Nees F Nees Frauke F Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany.
Papadopoulos Orfanos D Papadopoulos Orfanos Dimitri D NeuroSpin, CEA, Université Paris-Saclay, F-91191, Gif-sur-Yvette, France.
Paus T Paus Tomáš T Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital and Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, M6A 2E1, Canada.
Poustka L Poustka Luise L Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str. 5, 37075, Göttingen, Germany.
Sämann PG Sämann Philipp G PG Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Kraepelinstr, 2-10 80804, Munich, Germany.
Schofield PR Schofield Peter R PR Faculty of Medicine, University of New South Wales, Sydney, Australia.
Smolka MN Smolka Michael N MN Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
Stein DJ Stein Dan J DJ SAMRC Unit on Risk & Resilience in Mental Disorders, Cape Town, South Africa.
Strike LT Strike Lachlan T LT Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
Teeuw J Teeuw Jalmar J Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Thalamuthu A Thalamuthu Anbupalam A Neuroscience Research Australia, Sydney, NSW, Australia.
Trollor J Trollor Julian J Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Walter H Walter Henrik H Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charitéplatz 1, Berlin, Germany.
Wardlaw JM Wardlaw Joanna M JM UK Dementia Research Institute at the University of Edinburgh, Edinburgh, UK.
Wen W Wen Wei W Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Whelan R Whelan Robert R School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.
Apostolova LG Apostolova Liana G LG Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Binder EB Binder Elisabeth B EB Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Kraepelinstr, 2-10 80804, Munich, Germany.
Boomsma DI Boomsma Dorret I DI Vrije Universiteit, Amsterdam, Dept Biological Psychology, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
Calhoun V Calhoun Vince V Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Emory University, 30303, Atlanta, GA, USA.
Crespo-Facorro B Crespo-Facorro Benedicto B Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria, Santander, Spain.
Deary IJ Deary Ian J IJ Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Hulshoff Pol H Hulshoff Pol Hilleke H Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Ophoff RA Ophoff Roel A RA Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
Pausova Z Pausova Zdenka Z Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Sachdev PS Sachdev Perminder S PS Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia.
Saykin A Saykin Andrew A Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Wright MJ Wright Margaret J MJ Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Thompson PM Thompson Paul M PM 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.
Schumann G Schumann Gunter G Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Desrivières S Desrivières Sylvane S Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. sylvane.desrivieres@kcl.ac.uk.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2019
MONTH: Dec
DAY: 06
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
MR/R00465X/1 RCUK | MRC | Medical Research Foundation
MR/R00465X/1 RCUK | Medical Research Council (MRC)
MR/N000390/1 RCUK | Medical Research Council (MRC)
MR/N027558/1 RCUK | Medical Research Council (MRC)
MR/N000390/1 RCUK | Medical Research Council (MRC)
81801773 National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund)
18PJ1400900 Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission)
No.2018SHZDZX01 Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission)
No.16JC1420402 Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission)
259-2012-23 Svenska Forskningsrådet Formas (Swedish Research Council Formas)
R56 AG058854 NIA NIH HHS United States
U54 EB020403 NIBIB NIH HHS United States
LSHM-CT- 2007-037286 EC | Sixth Framework Programme (EC Sixth Framework Programme)
695313 EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
603016 EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health)
115300-2 EC | EC Seventh Framework Programm | FP7 Joint Technology Initiatives (FP7-JTI - Specific Programme "Cooperation": Joint Technology Initiatives)
NO.B18015 National Natural Science Foundation of China (National Science Foundation of China)
GENERAL NOTE
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