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

Jia, Tianye; Chu, Congying; Liu, Yun; van Dongen, Jenny; Papastergios, Evangelos; Armstrong, Nicola J.; Bastin, Mark E.; Carrillo Roa, Tania; den Braber, Anouk; Harris, Mathew; Jansen, Rick; Liu, Jingyu; Luciano, Michelle; Ori, Anil P. S.; Santianez, Roberto Roiz; Ruggeri, Barbara; Sarkisyan, Daniil; Shin, Jean; Sungeun, Kim; Gutierrez, Diana Tordesillas; van't Ent, Dennis; Ames, David; Artiges, Eric; Bakalkin, Georgy; Banaschewski, Tobias; Bokde, Arun L. W.; Brodaty, Henry; Bromberg, Uli; Brouwer, Rachel; Buchel, Christian; Quinlan, Erin Burke; Cahn, Wiepke; de Zubicaray I, Greig; Ehrlich, Stefan; Ekstrom, Tomas J.; Flor, Herta; Frohner, Juliane H.; Frouin, Vincent; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Hoare, Jacqueline; Ittermann, Bernd; Jahanshad, Neda; Jiang, Jiyang; Kwok, John B.; Martin, Nicholas G.; Martinot, Jean-Luc; Mather, Karen A.; McMahon, Katie L.; McRae, Allan F.; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Paus, Tomas; Poustka, Luise; Samann, Philipp G.; Schofield, Peter R.; Smolka, Michael N.; Stein, Dan J.; Strike, Lachlan T.; Teeuw, Jalmar; Thalamuthu, Anbupalam; Trollor, Julian; Walter, Henrik; Wardlaw, Joanna M.; Wen, Wei; Whelan, Robert; Apostolova, Liana G.; Binder, Elisabeth B.; Boomsma I, Dorret; Calhoun, Vince; Crespo-Facorro, Benedicto; Deary, Ian J.; Pol, Hilleke Hulshoff; Ophoff, Roel A.; Pausova, Zdenka; Sachdev, Perminder S.; Saykin, Andrew; Wright, Margaret J.; Thompson, Paul M.; Schumann, Gunter; Desrivieres, Sylvane

doi:10.1038/s41380-019-0605-z

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

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

MPS-Authors

/persons/resource/persons138194

Carrillo Roa, Tania
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80505

Samann, Philipp G.
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80272

Binder, Elisabeth B.
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Jia, T., Chu, C., Liu, Y., van Dongen, J., Papastergios, E., Armstrong, N. J., et al. (2021). Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group. MOLECULAR PSYCHIATRY, 26(8), 3884-3895. doi:10.1038/s41380-019-0605-z.

Cite as: https://hdl.handle.net/21.11116/0000-0009-F860-3

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.