title: Alcohol and tobacco consumption alter hypothalamic pituitary adrenal axis DNA methylation.
abstract: Alcohol and cigarette consumption have profound effects on genome wide DNA methylation and are common, often cryptic, comorbid features of many psychiatric disorders. This cryptic consumption is a possible impediment to understanding the biology of certain psychiatric disorders because if the effects of substance use are not taken into account, their presence may confound efforts to identify effects of other behavioral disorders. Since the hypothalamic pituitary adrenal (HPA) axis is known to be dysregulated in these disorders, we examined the potential for confounding effects of alcohol and cigarette consumption by examining their effects on peripheral DNA methylation at two key HPA axis genes, NR3C1 and FKBP5. We found that the influence of alcohol and smoke exposure is more prominent at the FKBP5 gene than the NR3C1 gene. Furthermore, in both genes, loci that were consistently significantly associated with smoking and alcohol consumption demethylated with increasing exposure. We conclude that epigenetic studies of complex disorders involving the HPA axis need to carefully control for the effects of substance use in order to minimize the possibility of type I and type II errors.
authors.affiliation: Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA; Department of Psychiatry, University of Iowa, Iowa City, IA, USA. Electronic address: meeshanthini-vijayendran@uiowa.edu.
authors.forename: Meeshanthini V
authors.initials: MV
authors.lastname: Dogan
authors.affiliation: Center for Family Research, University of Georgia, Athens, GA, USA. Electronic address: karlo@uga.edu.
authors.forename: Man-Kit
authors.initials: MK
authors.lastname: Lei
authors.affiliation: Center for Family Research, University of Georgia, Athens, GA, USA. Electronic address: srhbeach@uga.edu.
authors.forename: Steven R H
authors.initials: SR
authors.lastname: Beach
authors.affiliation: Center for Family Research, University of Georgia, Athens, GA, USA. Electronic address: gbrody@uga.edu.
authors.forename: Gene H
authors.initials: GH
authors.lastname: Brody
authors.affiliation: Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA; Department of Psychiatry, University of Iowa, Iowa City, IA, USA. Electronic address: robert-philibert@uiowa.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Philibert
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics*; D015331:Cohort Studies; D019175:DNA Methylation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D064424:Tobacco Use / Q000235:genetics*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D000431:Ethanol; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C497713:NR3C1 protein, human
keywords: DNA methylation; Drinking; Epigenetics; Hypothalamic pituitary adrenal axis; Psychiatric disorders; Smoking
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