Journal article
Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: Findings from the ENIGMA Epigenetics Working Group
Molecular Psychiatry, Vol.26, pp.3884-3895
2019
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.
Details
- Title
- Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: Findings from the ENIGMA Epigenetics Working Group
- Authors/Creators
- T. Jia (Author/Creator)C. Chu (Author/Creator)Y. Liu (Author/Creator)J. van Dongen (Author/Creator)E. Papastergios (Author/Creator)N.J. Armstrong (Author/Creator)M.E. Bastin (Author/Creator)T. Carrillo-Roa (Author/Creator)A. den Braber (Author/Creator)M. Harris (Author/Creator)R. Jansen (Author/Creator)J. Liu (Author/Creator)M. Luciano (Author/Creator)A.P.S. Ori (Author/Creator)R. Roiz Santiañez (Author/Creator)B. Ruggeri (Author/Creator)D. Sarkisyan (Author/Creator)J. Shin (Author/Creator)K. Sungeun (Author/Creator)D. Tordesillas Gutiérrez (Author/Creator)D. van’t Ent (Author/Creator)D. Ames (Author/Creator)E. Artiges (Author/Creator)G. Bakalkin (Author/Creator)T. Banaschewski (Author/Creator)A.L.W. Bokde (Author/Creator)H. Brodaty (Author/Creator)U. Bromberg (Author/Creator)R. Brouwer (Author/Creator)C. Büchel (Author/Creator)E. Burke Quinlan (Author/Creator)W. Cahn (Author/Creator)G.I. de Zubicaray (Author/Creator)S. Ehrlich (Author/Creator)T.J. Ekström (Author/Creator)H. Flor (Author/Creator)J.H. Fröhner (Author/Creator)V. Frouin (Author/Creator)H. Garavan (Author/Creator)P. Gowland (Author/Creator)A. Heinz (Author/Creator)J. Hoare (Author/Creator)B. Ittermann (Author/Creator)N. Jahanshad (Author/Creator)J. Jiang (Author/Creator)J.B. Kwok (Author/Creator)N.G. Martin (Author/Creator)J-L Martinot (Author/Creator)K.A. Mather (Author/Creator)K.L. McMahon (Author/Creator)A.F. McRae (Author/Creator)F. Nees (Author/Creator)D. Papadopoulos Orfanos (Author/Creator)T. Paus (Author/Creator)L. Poustka (Author/Creator)P.G. Sämann (Author/Creator)P.R. Schofield (Author/Creator)M.N. Smolka (Author/Creator)D.J. Stein (Author/Creator)L.T. Strike (Author/Creator)J. Teeuw (Author/Creator)A. Thalamuthu (Author/Creator)J. Trollor (Author/Creator)H. Walter (Author/Creator)J.M. Wardlaw (Author/Creator)W. Wen (Author/Creator)R. Whelan (Author/Creator)L.G. Apostolova (Author/Creator)E.B. Binder (Author/Creator)D.I. Boomsma (Author/Creator)V. Calhoun (Author/Creator)B. Crespo-Facorro (Author/Creator)I.J. Deary (Author/Creator)H.E. Hulshoff Pol (Author/Creator)R.A. Ophoff (Author/Creator)Z. Pausova (Author/Creator)P.S. Sachdev (Author/Creator)A. Saykin (Author/Creator)M.J. Wright (Author/Creator)P.M. Thompson (Author/Creator)G. Schumann (Author/Creator)S. Desrivières (Author/Creator)
- Publication Details
- Molecular Psychiatry, Vol.26, pp.3884-3895
- Publisher
- Nature Publishing Group
- Identifiers
- 991005543735207891
- Copyright
- © 2019 The Author(s).
- Murdoch Affiliation
- Information Technology, Mathematics and Statistics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.54 Molecular & Cell Biology - Genetics
- 1.54.100 Epigenetic Regulation
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences
- Psychiatry
- ESI research areas
- Neuroscience & Behavior