Array-Based Profiling of DNA Methylation Changes Associated with Alcohol Dependence
Article first published online: 24 AUG 2012
Copyright © 2012 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue Supplement s1, pages E108–E115, January 2013
How to Cite
Zhang, H., Herman, A. I., Kranzler, H. R., Anton, R. F., Zhao, H., Zheng, W. and Gelernter, J. (2013), Array-Based Profiling of DNA Methylation Changes Associated with Alcohol Dependence. Alcoholism: Clinical and Experimental Research, 37: E108–E115. doi: 10.1111/j.1530-0277.2012.01928.x
- Issue published online: 15 JAN 2013
- Article first published online: 24 AUG 2012
- Manuscript Accepted: 5 JUN 2012
- Manuscript Received: 26 JAN 2012
- National Institute of Health (NIH). Grant Numbers: K99/R00 DA022891, R01 DA12690, R01 AA11330, R01 DA12849, R01 AA017535, R01 DA018432, P50 AA027844, R01 DA011717, K05 AA017435
- VA CT MIRECC Center
- Alcoholic Beverage Medical Research Foundation (ABMRF)
- Illumina GoldenGate Methylation Array;
- Sequenom MassARRAY EpiTYPER;
- Promoter CpGs;
- Alcohol Dependence;
- Peripheral Blood DNA
Epigenetic regulation through DNA methylation may influence vulnerability to numerous disorders, including alcohol dependence (AD).
Peripheral blood DNA methylation levels of 384 CpGs in the promoter regions of 82 candidate genes were examined in 285 African Americans (AAs; 141 AD cases and 144 controls) and 249 European Americans (EAs; 144 AD cases and 105 controls) using Illumina GoldenGate Methylation Array assays. Association of AD and DNA methylation changes was analyzed using multivariate analyses of covariance with frequency of intoxication, sex, age, and ancestry proportion as covariates. CpGs showing significant methylation alterations in AD cases were further examined in a replication sample (49 EA cases and 32 EA controls) using Sequenom's MassARRAY EpiTYPER technology.
In AAs, 2 CpGs in 2 genes (GABRB3 and POMC) were hypermethylated in AD cases compared with controls (p ≤ 0.001). In EAs, 6 CpGs in 6 genes (HTR3A, NCAM1, DRD4, MBD3, HTR2B, and GRIN1) were hypermethylated in AD cases compared with controls (p ≤ 0.001); CpG cg08989585 in the HTR3A promoter region showed a significantly higher methylation level in EA cases than in EA controls after Bonferroni correction (p = 0.00007). Additionally, methylation levels of 6 CpGs (including cg08989585) in the HTR3A promoter region were analyzed in the replication sample. Although the 6 HTR3A promoter CpGs did not show significant methylation differences between EA cases and EA controls (p = 0.067 to 0.877), the methylation level of CpG cg08989585 was nonsignificantly higher in EA cases (26.9%) than in EA controls (18.6%; p = 0.139).
The findings from this study suggest that DNA methylation profile appears to be associated with AD in a population-specific way and the predisposition to AD may result from a complex interplay of genetic variation and epigenetic modifications.