@article{Jia2019, abstract = {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.}, author = {Jia, Tianye and Chu, Congying and Liu, Yun and van Dongen, Jenny and Papastergios, Evangelos and Armstrong, Nicola J. and Bastin, Mark E. and Carrillo-Roa, Tania and den Braber, Anouk and Harris, Mathew and Jansen, Rick and Liu, Jingyu and Luciano, Michelle and Ori, Anil P. S. and Santiañez, R. R. and Roiz Santiañez, Roberto and Ruggeri, Barbara and Sarkisyan, Daniil and Shin, Jean and Sungeun, Kim and Gutiérrez, D. T. and Tordesillas Gutiérrez, Diana and van’t Ent, Dennis and Ames, David and Artiges, Eric and Bakalkin, Georgy and Banaschewski, Tobias and Bokde, Arun L. W. and Brodaty, Henry and Bromberg, Uli and Brouwer, Rachel and Büchel, Christian and Burke Quinlan, Erin and Quinlan, E. B. and Cahn, Wiepke and de Zubicaray, Greig I. and Ehrlich, Stefan and Ekström, Tomas J. and Flor, Herta and Fröhner, Juliane H. and Frouin, Vincent and Garavan, Hugh and Gowland, Penny and Heinz, Andreas and Hoare, Jacqueline and Ittermann, Bernd and Jahanshad, Neda and Jiang, Jiyang and Kwok, John B. and Martin, Nicholas G. and Martinot, Jean-Luc and Mather, Karen A. and McMahon, Katie L. and McRae, Allan F. and Nees, Frauke and Orfanos, D. P. and Papadopoulos Orfanos, Dimitri and Paus, Tomáš and Poustka, Luise and Sämann, Philipp G. and Schofield, Peter R. and Smolka, Michael N. and Stein, Dan J. and Strike, Lachlan T. and Teeuw, Jalmar and Thalamuthu, Anbupalam and Trollor, Julian and Walter, Henrik and Wardlaw, Joanna M. and Wen, Wei and Whelan, Robert and Apostolova, Liana G. and Binder, Elisabeth B. and Boomsma, Dorret I. and Calhoun, Vince and Crespo-Facorro, Benedicto and Deary, Ian J. and Pol, H. H. and Hulshoff Pol, Hilleke and Ophoff, Roel A. and Pausova, Zdenka and Sachdev, Perminder S. and Saykin, Andrew and Wright, Margaret J. and Thompson, Paul M. and Schumann, Gunter and Desrivières, Sylvane}, doi = {10.1038/s41380-019-0605-z}, journal = {Molecular Psychiatry}, month = {dec}, pages = {3884-3895}, title = {Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group}, url = {https://www.nature.com/articles/s41380-019-0605-z.pdf}, volume = {26}, year = {2019} }