Alcohol and nicotine codependence-associated DNA methylation changes in promoter regions of addiction-related genes.
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.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Hongqin
H
Xu
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Fan
F
Wang
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and VISN4 MIRECC, Crescenz VAMC, Philadelphia, PA, USA.
Henry R
HR
Kranzler
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 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.
Joel
J
Gelernter
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.|VA Connecticut Healthcare System, West Haven, CT, USA.
Huiping
H
Zhang
D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D016022:Case-Control Studies; D017004:Codependency, Psychological; D019295:Computational Biology / Q000379:methods; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D009538:Nicotine / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044403:Receptor, Serotonin, 5-HT2B / Q000235:genetics; D019966:Substance-Related Disorders / Q000235:genetics* / Q000378:metabolism
C000628501:HTR2B protein, human; D006657:Histones; D044403:Receptor, Serotonin, 5-HT2B; D009538:Nicotine