Considering that AUDs are complex disorders affected by multiple genes and gene–environment interactions, we may be certain that the above candidate gene studies missed a number of important susceptibility genes for AUDs. To circumvent this issue, we examined peripheral blood DNA methylation levels of 384 CpGs in promoter regions of 82 addiction-related genes in 285 African Americans (AAs; 141 AUD cases and 144 controls) and 249 European Americans (EAs; 144 AUD cases and 105 controls) using a custom-designed Illumina GoldenGate DNA methylation array. In African American AUD subjects, two promoter CpGs in two genes (the γ-aminobutyric acid receptor subunit beta 3 gene [GABRB3] and POMC) were hypermethylated; while in European American AUD subjects, six promoter CpGs in six genes (the serotonin receptor 3A gene [HTR3A], the neural cell adhesion molecule 1 gene [NCAM1], the dopamine receptor D4 gene [DRD4], the methyl-CpG binding domain protein 3 gene [MBD3], the serotonin receptor 2B gene [HTR2B], and the NMDA receptor subtype 1 gene [GRIN1]) were hypermethylated. A specific CpG site in the HTR3A promoter region showed a significantly higher methylation level in EA
