Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence.
Weida Meng, Louise K Sjöholm, Olga Kononenko, Nicole Tay, Dandan Zhang, Daniil Sarkisyan, Jennifer R Geske, Alex Ing, Wenqing Qiu, Hiroyuki Watanabe, Radwa Almamoun, Helge Frieling, Stefan Bleich, Donghong Cui, Joanna M Biernacka, R Dayne Mayfield, Yongjun Dang, Victor M Karpyak, Gunter Schumann, IMAGEN Consortium, Georgy Bakalkin, Tomas J Ekström, Joelle Rüegg, Yun Liu
Molecular psychiatry 2021 AugAlcohol 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. © 2019. The Author(s), under exclusive licence to Springer Nature Limited.
Citation
Weida Meng, Louise K Sjöholm, Olga Kononenko, Nicole Tay, Dandan Zhang, Daniil Sarkisyan, Jennifer R Geske, Alex Ing, Wenqing Qiu, Hiroyuki Watanabe, Radwa Almamoun, Helge Frieling, Stefan Bleich, Donghong Cui, Joanna M Biernacka, R Dayne Mayfield, Yongjun Dang, Victor M Karpyak, Gunter Schumann, IMAGEN Consortium, Georgy Bakalkin, Tomas J Ekström, Joelle Rüegg, Yun Liu. Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence. Molecular psychiatry. 2021 Aug;26(8):4367-4382
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PMID: 31745236
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