Mouse and human genetic analyses associate Kalirin with ventral striatal activation during impulsivity and with alcohol misuse
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Published: |
Frontiers Media
2016
|
| Subjects: | |
| Online Access: | https://eprints.nottingham.ac.uk/39588/ |
| _version_ | 1848795871126224896 |
|---|---|
| author | Peña-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. Büchel, Christian Conrod, Patricia J. Flor, Herta Gallinat, Jürgen Garavan, Hugh Heinz, Andreas Gowland, Penny A. Paillere Martinot, Marie-Laure Paus, Tomáš Rietschel, Marcella Robbins, Trevor W. Smolka, Michael N. Schumann, Gunter Stephens, David N. |
| author_facet | Peña-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. Büchel, Christian Conrod, Patricia J. Flor, Herta Gallinat, Jürgen Garavan, Hugh Heinz, Andreas Gowland, Penny A. Paillere Martinot, Marie-Laure Paus, Tomáš Rietschel, Marcella Robbins, Trevor W. Smolka, Michael N. Schumann, Gunter Stephens, David N. |
| author_sort | Peña-Oliver, Yolanda |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:38:58Z |
| format | Article |
| id | nottingham-39588 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:38:58Z |
| publishDate | 2016 |
| publisher | Frontiers Media |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-395882020-05-04T17:47:29Z https://eprints.nottingham.ac.uk/39588/ Mouse and human genetic analyses associate Kalirin with ventral striatal activation during impulsivity and with alcohol misuse Peña-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. Büchel, Christian Conrod, Patricia J. Flor, Herta Gallinat, Jürgen Garavan, Hugh Heinz, Andreas Gowland, Penny A. Paillere Martinot, Marie-Laure Paus, Tomáš Rietschel, Marcella Robbins, Trevor W. Smolka, Michael N. Schumann, Gunter Stephens, David N. 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. Frontiers Media 2016-04-07 Article PeerReviewed Peña-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., Büchel, Christian, Conrod, Patricia J., Flor, Herta, Gallinat, Jürgen, Garavan, Hugh, Heinz, Andreas, Gowland, Penny A., Paillere Martinot, Marie-Laure, Paus, Tomáš, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Schumann, Gunter and Stephens, David N. (2016) Mouse and human genetic analyses associate Kalirin with ventral striatal activation during impulsivity and with alcohol misuse. Frontiers in Genetics, 7 . 52/1-52/14. ISSN 1664-8021 impulsivity binge drinking adolescent fMRI BXD recombinant inbred strains monetary incentive delay 5-choice serial reaction time task http://journal.frontiersin.org/article/10.3389/fgene.2016.00052/full doi:10.3389/fgene.2016.00052 doi:10.3389/fgene.2016.00052 |
| spellingShingle | impulsivity binge drinking adolescent fMRI BXD recombinant inbred strains monetary incentive delay 5-choice serial reaction time task Peña-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. Büchel, Christian Conrod, Patricia J. Flor, Herta Gallinat, Jürgen Garavan, Hugh Heinz, Andreas Gowland, Penny A. Paillere Martinot, Marie-Laure Paus, Tomáš Rietschel, Marcella Robbins, Trevor W. Smolka, Michael N. Schumann, Gunter Stephens, David N. Mouse and human genetic analyses associate Kalirin with ventral striatal activation during impulsivity and with alcohol misuse |
| title | Mouse and human genetic analyses associate Kalirin with ventral striatal activation during impulsivity and with alcohol misuse |
| title_full | Mouse and human genetic analyses associate Kalirin with ventral striatal activation during impulsivity and with alcohol misuse |
| title_fullStr | Mouse and human genetic analyses associate Kalirin with ventral striatal activation during impulsivity and with alcohol misuse |
| title_full_unstemmed | Mouse and human genetic analyses associate Kalirin with ventral striatal activation during impulsivity and with alcohol misuse |
| title_short | Mouse and human genetic analyses associate Kalirin with ventral striatal activation during impulsivity and with alcohol misuse |
| title_sort | mouse and human genetic analyses associate kalirin with ventral striatal activation during impulsivity and with alcohol misuse |
| topic | impulsivity binge drinking adolescent fMRI BXD recombinant inbred strains monetary incentive delay 5-choice serial reaction time task |
| url | https://eprints.nottingham.ac.uk/39588/ https://eprints.nottingham.ac.uk/39588/ https://eprints.nottingham.ac.uk/39588/ |