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

被引：0

作者：

Tianye Jia

Congying Chu

Yun Liu

Jenny van Dongen

Evangelos Papastergios

Nicola J. Armstrong

Mark E. Bastin

Tania Carrillo-Roa

Anouk den Braber

Mathew Harris

Rick Jansen

Jingyu Liu

Michelle Luciano

Anil P. S. Ori

Roberto Roiz Santiañez

Barbara Ruggeri

Daniil Sarkisyan

Jean Shin

Kim Sungeun

Diana Tordesillas Gutiérrez

Dennis van’t Ent

David Ames

Eric Artiges

Georgy Bakalkin

Tobias Banaschewski

Arun L. W. Bokde

Henry Brodaty

Uli Bromberg

Rachel Brouwer

Christian Büchel

Erin Burke Quinlan

Wiepke Cahn

Greig I. de Zubicaray

Stefan Ehrlich

Tomas J. Ekström

Herta Flor

Juliane H. Fröhner

Vincent Frouin

Hugh Garavan

Penny Gowland

Andreas Heinz

Jacqueline Hoare

Bernd Ittermann

Neda Jahanshad

Jiyang Jiang

John B. Kwok

Nicholas G. Martin

Jean-Luc Martinot

Karen A. Mather

Katie L. McMahon

机构：

[1] Psychology & Neuroscience,Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry

[2] King’s College London,Institute of Science and Technology for Brain

[3] Fudan University,Inspired Intelligence

[4] Fudan University,MOE Key Laboratory of Computational Neuroscience and Brain

[5] Zhongshan Hospital,Inspired Intelligence

[6] Fudan University,MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences

[7] Vrije Universiteit,Mathematics and Statistics

[8] Amsterdam,Brain Research Imaging Centre, Centre for Clinical Brain Sciences, and Centre for Cognitive Ageing and Cognitive Epidemiology

[9] Dept Biological Psychology,Department of Translational Research in Psychiatry

[10] Murdoch University,Centre for Clinical Brain Sciences and Edinburgh Imaging

[11] University of Edinburgh (MEB),Department of Psychiatry

[12] Max-Planck Institute of Psychiatry,Department of Electrical Engineering

[13] Kraepelinstr,Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology

[14] University of Edinburgh,UCLA Center for Neurobehavioral Genetics

[15] VU University Medical Centre,Department of Psychiatry, University Hospital Marqués de Valdecilla

[16] University of New Mexico,Hospital for Sick Children

[17] University of Edinburgh,Center for Neuroimaging, Department of Radiology and Imaging Sciences

[18] University of California,Center for Computational Biology and Bioinformatics

[19] Los Angeles,Neuroimaging Unit

[20] School of Medicine,Academic Unit for Psychiatry of Old Age

[21] University of Cantabria,Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 “Neuroimaging & Psychiatry”

[22] Centro Investigación Biomédica en Red de Salud Mental,Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim

[23] Box 591,Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience

[24] Uppsala biomedicinska centrum BMC,Centre for Healthy Brain Ageing, School of Psychiatry

[25] Husarg. 3,Dementia Centre for Research Collaboration, School of Psychiatry

[26] 751 24,Department of Psychiatry and Brain Center Rudolf Magnus

[27] University of Toronto,Faculty of Health, Institute of Health and Biomedical Innovation

[28] Indiana University School of Medicine,Division of Psychological and Social Medicine and Developmental Neurosciences

[29] Indiana University School of Medicine,Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine

[30] Technological Facilities. Valdecilla Biomedical Research Institute IDIVAL,Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim

[31] National Ageing Research Institute,Department of Psychology, School of Social Sciences

[32] University of Melbourne,Department of Psychiatry and Neuroimaging Center

[33] St George’s Hospital,Departments of Psychiatry and Psychology

[34] University Paris Sud-Paris Saclay,Sir Peter Mansfield Imaging Centre School of Physics and Astronomy

[35] University Paris Descartes,Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin

[36] DIGITEO Labs,Berlin Institute of Health, Department of Psychiatry and Psychotherapy

[37] GH Nord Essonne Psychiatry Department 91G16,Department of Psychiatry and Neuroscience Institute

[38] Heidelberg University,Physikalisch

[39] Square J5,Technische Bundesanstalt (PTB)

[40] Trinity College Dublin,Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute

[41] University of New South Wales,Central Clinical School—Brain and Mind Centre

[42] University of New South Wales,School of Medical Sciences

[43] University Medical Centre Hamburg-Eppendorf,Maison de Solenn

[44] House W34,Herston Imaging Research Facility, School of Clinical Sciences

[45] University Medical Center Utrecht,Institute for Molecular Bioscience

[46] Queensland University of Technology,Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital and Departments of Psychology and Psychiatry

[47] Faculty of Medicine,Department of Child and Adolescent Psychiatry and Psychotherapy

[48] Karolinska University Hospital,Faculty of Medicine

[49] Heidelberg University,Queensland Brain Institute

[50] Square J5,Department of Developmental Disability Neuropsychiatry, School of Psychiatry

来源：

Molecular Psychiatry | 2021年 / 26卷

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中图分类号：

学科分类号：

摘要：

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.

引用

页码：3884 / 3895

页数：11

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