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