TY  - JOUR
A1  - Clarke, Toni-Kim
A1  - Laucht, Manfred
A1  - Ridinger, Monika
A1  - Wodarz, Norbert
A1  - Rietschel, Marcella
A1  - Maier, Wolfgang
A1  - Lathrop, Mark
A1  - Lourdusamy, Anbarasu
A1  - Zimmermann, Ulrich S.
A1  - Desrivieres, Sylvane
A1  - Schumann, Gunter
T1  - KCNJ6 is associated with adult alcohol dependence and involved in gene x early life stress interactions in adolescent alcohol drinking
JF  - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
N2  - Alcohol abuse and dependence have proven to be complex genetic traits that are influenced by environmental factors. Primate and human studies have shown that early life stress increases the propensity for alcohol abuse in later life. The reinforcing properties of alcohol are mediated by dopaminergic signaling; however, there is little evidence to indicate how stress alters alcohol reinforcement. KCNJ6 (the gene encoding G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2)) is a brain expressed potassium channel with inhibitory effects on dopaminergic tone. The properties of GIRK2 have been shown to be enhanced by the stress peptide corticotrophin-releasing hormone. Therefore, we sought to examine the role of KCNJ6 polymorphisms in adult alcohol dependence and stress-related alcohol abuse in adolescents. We selected 11 SNPs in the promoter region of KCNJ6, which were genotyped in 1152 adult alcohol dependents and 1203 controls. One SNP, rs2836016, was found to be associated with alcohol dependence (p = 0.01, false discovery rate). We then assessed rs2836016 in an adolescent sample of 261 subjects, which were characterized for early life stress and adolescent hazardous drinking, defined using the Alcohol Use Disorders Identification Test (AUDIT), to examine gene-environment interactions. In the adolescent sample, the risk genotype of rs2836016 was significantly associated with increased AUDIT scores, but only in those individuals exposed to high levels of psychosocial stress in early life (p = 0.01). Our findings show that KCNJ6 is associated with alcohol dependence and may moderate the effect of early psychosocial stress on risky alcohol drinking in adolescents. We have identified a candidate gene for future studies investigating a possible functional link between the response to stress and alcohol reinforcement.
KW  - alcoholism
KW  - genetics
KW  - GIRK2
KW  - stress
KW  - gene x environment
KW  - KCNJ6
Y1  - 2011
U6  - https://doi.org/10.1038/npp.2010.247
SN  - 0893-133X
VL  - 36
IS  - 6
SP  - 1142
EP  - 1148
PB  - Nature Publ. Group
CY  - London
ER  -