title: Validation of differential GDAP1 DNA methylation in alcohol dependence and its potential function as a biomarker for disease severity and therapy outcome.
abstract: Alcohol dependence is a severe disorder contributing substantially to the global burden of disease. Despite the detrimental consequences of chronic alcohol abuse and dependence, effective prevention strategies as well as treatment options are largely missing to date. Accumulating evidence suggests that gene-environment interactions, including epigenetic mechanisms, play a role in the etiology of alcohol dependence. A recent epigenome-wide study reported widespread alterations of DNA methylation patterns in alcohol dependent patients compared to control individuals. In the present study, we validate and replicate one of the top findings from this previous investigation in an independent cohort: the hypomethylation of GDAP1 in patients. To our knowledge, this is the first independent replication of an epigenome-wide finding in alcohol dependence. Furthermore, the AUDIT as well as the GSI score were negatively associated with GDAP1 methylation and we found a trend toward a negative association between GDAP1 methylation and the years of alcohol dependency, pointing toward a potential role of GDAP1 hypomethylation as biomarker for disease severity. In addition, we show that the hypomethylation of GDAP1 in patients reverses during a short-term alcohol treatment program, suggesting that GDAP1 DNA methylation could also serve as a potential biomarker for treatment outcome. Our data add to the growing body of knowledge on epigenetic effects in alcohol dependence and support GDAP1 as a novel candidate gene implicated in this disorder. As the role of GDAP1 in alcohol dependence is unknown, this novel candidate gene should be followed up in future studies.
authors.affiliation: a Department of Psychiatry and Psychotherapy , University Hospital of Tuebingen , Tuebingen , Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Brückmann
authors.affiliation: a Department of Psychiatry and Psychotherapy , University Hospital of Tuebingen , Tuebingen , Germany.
authors.forename: Adriana
authors.initials: A
authors.lastname: Di Santo
authors.affiliation: a Department of Psychiatry and Psychotherapy , University Hospital of Tuebingen , Tuebingen , Germany.
authors.forename: Kathrin Nora
authors.initials: KN
authors.lastname: Karle
authors.affiliation: b Section for Addiction Medicine and Addiction Research, Department of Psychiatry and Psychotherapy, University Hospital of Tuebingen , Tuebingen , Germany.
authors.forename: Anil
authors.initials: A
authors.lastname: Batra
authors.affiliation: a Department of Psychiatry and Psychotherapy , University Hospital of Tuebingen , Tuebingen , Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nieratschker
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000097:blood / Q000235:genetics* / Q000628:therapy; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C118663:GDAP protein; D009419:Nerve Tissue Proteins
keywords: Alcohol dependence; DNA methylation; GDAP1; biomarker; disease severity; epigenetics; replication; treatment outcome; validation