Yolanda Pe�a-Oliver
Mouse and human genetic analyses associate Kalirin with ventral striatal activation during impulsivity and with alcohol misuse
Pe�a-Oliver, Yolanda; Carvalho, Fabiana M.; Sanchez-Roige, Sandra; Quinlan, Erin Burke; Jia, Tianye; Walker-Tilley, Tom; Rulten, Stuart L.; Pearl, Frances M. G.; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L. W.; B�chel, Christian; Conrod, Patricia J.; Flor, Herta; Gallinat, J�rgen; Garavan, Hugh; Heinz, Andreas; Gowland, Penny A.; Paillere Martinot, Marie-Laure; Paus, Tom�; Rietschel, Marcella; Robbins, Trevor W.; Smolka, Michael N.; Schumann, Gunter; Stephens, David N.
Authors
Fabiana M. Carvalho
Sandra Sanchez-Roige
Erin Burke Quinlan
Tianye Jia
Tom Walker-Tilley
Stuart L. Rulten
Frances M. G. Pearl
Tobias Banaschewski
Gareth J. Barker
Arun L. W. Bokde
Christian B�chel
Patricia J. Conrod
Herta Flor
J�rgen Gallinat
Hugh Garavan
Andreas Heinz
Penny A. Gowland
Marie-Laure Paillere Martinot
Tom� Paus
Marcella Rietschel
Trevor W. Robbins
Michael N. Smolka
Gunter Schumann
David N. Stephens
Abstract
Impulsivity is associated with a spectrum of psychiatric disorders including drug addiction. To investigate genetic associations with impulsivity and initiation of drug taking, we took a two-step approach. First, we identified genes whose expression level in prefrontal cortex, striatum and accumbens were associated with impulsive behavior in the 5-choice serial reaction time task across 10 BXD recombinant inbred (BXD RI) mouse strains and their progenitor C57BL/6J and DBA2/J strains. Behavioral data were correlated with regional gene expression using GeneNetwork (www.genenetwork.org), to identify 44 genes whose probability of association with impulsivity exceeded a false discovery rate of < 0.05. We then interrogated the IMAGEN database of 1423 adolescents for potential associations of SNPs in human homologs of those genes identified in the mouse study, with brain activation during impulsive performance in the Monetary Incentive Delay task, and with novelty seeking scores from the Temperament and Character Inventory, as well as alcohol experience. There was a significant overall association between the human homologs of impulsivity-related genes and percentage of premature responses in the MID task and with fMRI BOLD-response in ventral striatum (VS) during reward anticipation. In contrast, no significant association was found between the polygenic scores and anterior cingulate cortex activation. Univariate association analyses revealed that the G allele (major) of the intronic SNP rs6438839 in the KALRN gene was significantly associated with increased VS activation. Additionally, the A-allele (minor) of KALRN intronic SNP rs4634050, belonging to the same haplotype block, was associated with increased frequency of binge drinking.
Citation
Peña-Oliver, Y., Carvalho, F. M., Sanchez-Roige, S., Quinlan, E. B., Jia, T., Walker-Tilley, T., …Stephens, D. N. (2016). Mouse and human genetic analyses associate Kalirin with ventral striatal activation during impulsivity and with alcohol misuse. Frontiers in Genetics, 7, Article 52. https://doi.org/10.3389/fgene.2016.00052
Journal Article Type | Article |
---|---|
Acceptance Date | Mar 21, 2016 |
Publication Date | Apr 7, 2016 |
Deposit Date | Jan 5, 2017 |
Publicly Available Date | Jan 5, 2017 |
Journal | Frontiers in Genetics |
Electronic ISSN | 1664-8021 |
Publisher | Frontiers Media |
Peer Reviewed | Peer Reviewed |
Volume | 7 |
Article Number | 52 |
DOI | https://doi.org/10.3389/fgene.2016.00052 |
Keywords | impulsivity, binge drinking, adolescent, fMRI, BXD recombinant inbred strains, monetary incentive delay, 5-choice serial reaction time task |
Public URL | https://nottingham-repository.worktribe.com/output/786081 |
Publisher URL | http://journal.frontiersin.org/article/10.3389/fgene.2016.00052/full |
Contract Date | Jan 5, 2017 |
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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