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  - 
TY  - GEN
A1  - Kaminski, Jakob A.
A1  - Schlagenhauf, Florian
A1  - Rapp, Michael A.
A1  - Awasthi, Swapnil
A1  - Ruggeri, Barbara
A1  - Deserno, Lorenz
A1  - Banaschewski, Tobias
A1  - Bokde, Arun L. W.
A1  - Bromberg, Uli
A1  - Büchel, Christian
A1  - Quinlan, Erin Burke
A1  - Desrivières, Sylvane
A1  - Flor, Herta
A1  - Frouin, Vincent
A1  - Garavan, Hugh
A1  - Gowland, Penny
A1  - Ittermann, Bernd
A1  - Martinot, Jean-Luc
A1  - Paillère Martinot, Marie-Laure
A1  - Nees, Frauke
A1  - Papadopoulos Orfanos, Dimitri
A1  - Paus, Tomáš
A1  - Poustka, Luise
A1  - Smolka, Michael N.
A1  - Fröhner, Juliane H.
A1  - Walter, Henrik
A1  - Whelan, Robert
A1  - Ripke, Stephan
A1  - Schumann, Gunter
A1  - Heinz, Andreas
T1  - Epigenetic variance in dopamine D2 receptor
BT  - a marker of IQ malleability?
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 950 
KW  - genome-wide association
KW  - reward anticipation
KW  - human intelligence
KW  - human brain
KW  - stress
KW  - metaanalysis
KW  - striatum
KW  - psychopathology
KW  - prediction
KW  - volume
KW  - epigenetics and behaviour
KW  - human behaviour
KW  - learning and memory
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-425687
SN  - 1866-8372
IS  - 950
ER  -