Send to

Choose Destination
Sci Rep. 2017 Feb 6;7:41816. doi: 10.1038/srep41816.

Alcohol and nicotine codependence-associated DNA methylation changes in promoter regions of addiction-related genes.

Author information

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and VISN4 MIRECC, Crescenz VAMC, Philadelphia, PA, USA.
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA.
VA Connecticut Healthcare System, West Haven, CT, USA.


Altered DNA methylation in addiction-related genes may modify the susceptibility to alcohol or drug dependence (AD or ND). We profiled peripheral blood DNA methylation levels of 384 CpGs in promoter regions of 82 addiction-related genes in 256 African Americans (AAs) (117 cases with AD-ND codependence and 139 controls) and 196 European Americans (103 cases with AD-ND codependence and 93 controls) using Illumina's GoldenGate DNA methylation array assays. AD-ND codependence-associated DNA methylation changes were analyzed using linear mixed-effects models with consideration of batch effects and covariates age, sex, and ancestry proportions. Seventy CpGs (in 41 genes) showed nominally significant associations (P < 0.05) with AD-ND codependence in both AAs and EAs. One CpG (HTR2B cg27531267) was hypomethylated in AA cases (P = 7.2 × 10-5), while 17 CpGs in 16 genes (including HTR2B cg27531267) were hypermethylated in EA cases (5.6 × 10-9 ≤ P ≤ 9.5 × 10-5). Nevertheless, 13 single nucleotide polymorphisms (SNPs) nearby HTR2B cg27531267 and the interaction of these SNPs and cg27531267 did not show significant effects on AD-ND codependence in either AAs or EAs. Our study demonstrated that DNA methylation changes in addiction-related genes could be potential biomarkers for AD-ND co-dependence. Future studies need to explore whether DNA methylation alterations influence the risk of AD-ND codependence or the other way around.

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Although unrelated to this research, Dr. Kranzler has been a consultant, advisory board member, or CME speaker for Indivior, Lundbeck, and Otsuka. He is also a member of the Alcohol Clinical Trials Initiative of the American Society of Clinical Psychopharmacology, which is supported by AbbVie, Ethypharm, Lilly, Lundbeck, and Pfizer. Other authors declare that they have no competing interests.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center