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

dc.contributor.authorJia, Tianye
dc.contributor.authorChu, Congying
dc.contributor.authorLiu, Yun
dc.contributor.authorVan Dongen, Jenny
dc.contributor.authorPapastergios, Evangelos
dc.contributor.authorArmstrong, Nicola J.
dc.contributor.authorBastin, Mark E.
dc.contributor.authorCarrillo-Roa, Tania
dc.contributor.authorden Braber, Anouk
dc.contributor.authorHarris, Mathew
dc.contributor.authorJansen, Rick
dc.contributor.authorLiu, Jingyu
dc.contributor.authorLuciano, Michelle
dc.contributor.authorOri, Anil P.S.
dc.contributor.authorSantiañez, Roberto Roiz
dc.contributor.authorRuggeri, Barbara
dc.contributor.authorSarkisyan, Daniil
dc.contributor.authorShin, Jean
dc.contributor.authorSungeun, Kim
dc.contributor.authorTordesillas Gutiérrez, Diana
dc.contributor.authorvan't Ent, Dennis
dc.contributor.authorAmes, David
dc.contributor.authorArtiges, Eric
dc.contributor.authorBakalkin, Georgy
dc.contributor.authorBanaschewski, Tobias
dc.contributor.authorBokde, Arun L.W.
dc.contributor.authorBrodaty, Henry
dc.contributor.authorBromberg, Uli
dc.contributor.authorBrouwer, Rachel
dc.contributor.authorBüchel, Christian
dc.contributor.authorBurke Quinlan, Erin
dc.contributor.authorCahn, Wiepke
dc.contributor.authorde Zubicaray, Greig I.
dc.contributor.authorEhrlich, Stefan
dc.contributor.authorEkström, Tomas J.
dc.contributor.authorFlor, Herta
dc.contributor.authorFröhner, Juliane H.
dc.contributor.authorFrouin, Vincent
dc.contributor.authorGaravan, Hugh
dc.contributor.authorGowland, Penny
dc.contributor.authorHeinz, Andreas
dc.contributor.authorHoare, Jacqueline
dc.contributor.authorIttermann, Bernd
dc.contributor.authorJahanshad, Neda
dc.contributor.authorJiang, Jiyang
dc.contributor.authorKwok, John B.
dc.contributor.authorMartin, Nicholas G.
dc.contributor.authorMartinot, Jean-Luc
dc.contributor.authorMather, Karen A.
dc.contributor.authorMcMahon, Katie L.
dc.contributor.authorMcRae, Allan F.
dc.contributor.authorNees, Frauke
dc.contributor.authorOrfanos, Dimitri Papadopoulos
dc.contributor.authorPaus, Tomáš
dc.contributor.authorPoustka, Luise
dc.contributor.authorSämann, Philipp G.
dc.contributor.authorSchofield, Peter R.
dc.contributor.authorSmolka, Michael N.
dc.contributor.authorStein, Dan J.
dc.contributor.authorStrike, Lachlan T.
dc.contributor.authorTeeuw, Jalmar
dc.contributor.authorThalamuthu, Anbupalam
dc.contributor.authorTrollor, Julian
dc.contributor.authorWalter, Henrik
dc.contributor.authorWardlaw, Joanna M.
dc.contributor.authorWen, Wei
dc.contributor.authorWhelan, Robert
dc.contributor.authorApostolova, Liana G.
dc.contributor.authorBinder, Elisabeth B.
dc.contributor.authorBoomsma, Dorret I.
dc.contributor.authorCalhoun, Vince
dc.contributor.authorCrespo-Facorro, Benedicto
dc.contributor.authorDeary, Ian J.
dc.contributor.authorHulshoff Pol, Hilleke
dc.contributor.authorOphoff, Roel A.
dc.contributor.authorPausova, Zdenka
dc.contributor.authorSachdev, Perminder S.
dc.contributor.authorSaykin, Andrew
dc.contributor.authorWright, Margaret J.
dc.contributor.authorThompson, Paul M.
dc.contributor.authorSchumann, Gunter
dc.contributor.authorDesrivières, Sylvane
dc.contributor.departmentRadiology and Imaging Sciences, School of Medicine
dc.date.accessioned2023-03-31T11:28:52Z
dc.date.available2023-03-31T11:28:52Z
dc.date.issued2021
dc.description.abstractDNA 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.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationJia T, Chu C, Liu Y, et al. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group. Mol Psychiatry. 2021;26(8):3884-3895. doi:10.1038/s41380-019-0605-zen_US
dc.identifier.urihttps://hdl.handle.net/1805/32153
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.isversionof10.1038/s41380-019-0605-zen_US
dc.relation.journalMolecular Psychiatryen_US
dc.rightsAttribution 4.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.sourcePMCen_US
dc.subjectGeneticsen_US
dc.subjectMolecular biologyen_US
dc.subjectNeuroscienceen_US
dc.titleEpigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Groupen_US
dc.typeArticleen_US
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