TY - JOUR
T1 - Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence
AU - IMAGEN Consortium
AU - Meng, Weida
AU - Sjöholm, Louise K.
AU - Kononenko, Olga
AU - Tay, Nicole
AU - Zhang, Dandan
AU - Sarkisyan, Daniil
AU - Geske, Jennifer R.
AU - Ing, Alex
AU - Qiu, Wenqing
AU - Watanabe, Hiroyuki
AU - Almamoun, Radwa
AU - Frieling, Helge
AU - Bleich, Stefan
AU - Cui, Donghong
AU - Biernacka, Joanna M.
AU - Mayfield, R. Dayne
AU - Dang, Yongjun
AU - Karpyak, Victor M.
AU - Schumann, Gunter
AU - Banaschewski, Tobias
AU - Barker, Gareth J.
AU - Bokde, Arun L.W.
AU - Quinlan, Erin Burke
AU - Desrivières, Sylvane
AU - Flor, Herta
AU - Grigis, Antoine
AU - Garavan, Hugh
AU - Gowland, Penny
AU - Heinz, Andreas
AU - Ittermann, Bernd
AU - Martinot, Jean Luc
AU - Martinot, Marie Laure Paillère
AU - Artiges, Eric
AU - Nees, Frauke
AU - Orfanos, Dimitri Papadopoulos
AU - Lemaitre, Herve
AU - Paus, Tomáš
AU - Poustka, Luise
AU - Hohmann, Sarah
AU - Millenet, Sabina
AU - Fröhner, Juliane H.
AU - Smolka, Michael N.
AU - Walter, Henrik
AU - Whelan, Robert
AU - Bakalkin, Georgy
AU - Ekström, Tomas J.
AU - Rüegg, Joelle
AU - Liu, Yun
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/8
Y1 - 2021/8
N2 - Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.
AB - Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.
UR - http://www.scopus.com/inward/record.url?scp=85075230843&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85075230843&partnerID=8YFLogxK
U2 - 10.1038/s41380-019-0588-9
DO - 10.1038/s41380-019-0588-9
M3 - Article
C2 - 31745236
AN - SCOPUS:85075230843
SN - 1359-4184
VL - 26
SP - 4367
EP - 4382
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 8
ER -