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A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response

A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response
A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response
The TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster in smoking and their association with smoking-associated reward processing in adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported smoking behaviours was performed in four European adolescent cohorts (N = 14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self-reported smoking (p = 5.0 × 10-4) and higher plasma cotinine levels (p = 7.0 × 10-5). This risk allele was linked to an increased ventral-striatal blood-oxygen level-dependent (BOLD) response during reward anticipation (n = 1,263) and with higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene-cluster in adolescent smoking behaviours, provide evidence for the involvement of DRD2 in the early stages of addiction and support the notion that genetically-driven inter-individual differences in dopaminergic transmission mediate reward sensitivity and risk to smoking.
0924-977X
1103-1114
MacAre, Christine
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Ducci, Francesca
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Zhang, Yuning
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Ruggeri, Barbara
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Jia, Tianye
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Kaakinen, Marika
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Kalsi, Gursharan
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Charoen, Pimphen
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Casoni, Filippo
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Peters, Jan
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Bromberg, Uli
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Hill, Matthew
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Buxton, Jessica L
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Blakemore, Alexandra I.F.
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Veijola, Juha
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Büchel, Christian
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Banaschewski, Tobias
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Bokde, Arun
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Conrod, Patricia
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Flor, Herta
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Frouin, Vincent
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Gallinat, Jürgen
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Garavan, Hugh
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Gowland, Penny
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Heinz, Andreas
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Ittermann, Bernd
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Lathrop, Mark G.
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Martinot, Jean-Luc
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Paus, Tomáš
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Desrivieres, Sylvane
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Munafò, Marcus R.
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Järvelin, Marjo-Riitta
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Schumann, Gunter
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The IMAGEN Consortium
MacAre, Christine
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Ducci, Francesca
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Zhang, Yuning
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Ruggeri, Barbara
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Jia, Tianye
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Kaakinen, Marika
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Kalsi, Gursharan
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Charoen, Pimphen
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Casoni, Filippo
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Peters, Jan
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Bromberg, Uli
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Hill, Matthew
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Buxton, Jessica L
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Blakemore, Alexandra I.F.
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Veijola, Juha
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Büchel, Christian
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Banaschewski, Tobias
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Bokde, Arun
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Conrod, Patricia
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Flor, Herta
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Frouin, Vincent
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Gallinat, Jürgen
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Garavan, Hugh
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Gowland, Penny
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Heinz, Andreas
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Ittermann, Bernd
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Lathrop, Mark G.
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Martinot, Jean-Luc
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Paus, Tomáš
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Desrivieres, Sylvane
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Munafò, Marcus R.
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Järvelin, Marjo-Riitta
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Schumann, Gunter
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MacAre, Christine, Ducci, Francesca, Zhang, Yuning, Ruggeri, Barbara, Jia, Tianye, Kaakinen, Marika, Kalsi, Gursharan, Charoen, Pimphen, Casoni, Filippo, Peters, Jan, Bromberg, Uli, Hill, Matthew, Buxton, Jessica L, Blakemore, Alexandra I.F., Veijola, Juha, Büchel, Christian, Banaschewski, Tobias, Bokde, Arun, Conrod, Patricia, Flor, Herta, Frouin, Vincent, Gallinat, Jürgen, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lathrop, Mark G., Martinot, Jean-Luc, Paus, Tomáš, Desrivieres, Sylvane, Munafò, Marcus R., Järvelin, Marjo-Riitta and Schumann, Gunter , The IMAGEN Consortium (2018) A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response. European Neuropsychopharmacology, 28 (10), 1103-1114. (doi:10.1016/j.euroneuro.2018.07.101).

Record type: Article

Abstract

The TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster in smoking and their association with smoking-associated reward processing in adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported smoking behaviours was performed in four European adolescent cohorts (N = 14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self-reported smoking (p = 5.0 × 10-4) and higher plasma cotinine levels (p = 7.0 × 10-5). This risk allele was linked to an increased ventral-striatal blood-oxygen level-dependent (BOLD) response during reward anticipation (n = 1,263) and with higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene-cluster in adolescent smoking behaviours, provide evidence for the involvement of DRD2 in the early stages of addiction and support the notion that genetically-driven inter-individual differences in dopaminergic transmission mediate reward sensitivity and risk to smoking.

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Accepted/In Press date: 17 July 2018
e-pub ahead of print date: 11 August 2018
Published date: October 2018

Identifiers

Local EPrints ID: 437745
URI: http://eprints.soton.ac.uk/id/eprint/437745
ISSN: 0924-977X
PURE UUID: 1b35edc3-6079-450b-af1a-6c8d73c7576e
ORCID for Yuning Zhang: ORCID iD orcid.org/0000-0003-2225-6368

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Date deposited: 13 Feb 2020 17:32
Last modified: 15 Jul 2020 00:46

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Contributors

Author: Christine MacAre
Author: Francesca Ducci
Author: Yuning Zhang ORCID iD
Author: Barbara Ruggeri
Author: Tianye Jia
Author: Marika Kaakinen
Author: Gursharan Kalsi
Author: Pimphen Charoen
Author: Filippo Casoni
Author: Jan Peters
Author: Uli Bromberg
Author: Matthew Hill
Author: Jessica L Buxton
Author: Alexandra I.F. Blakemore
Author: Juha Veijola
Author: Christian Büchel
Author: Tobias Banaschewski
Author: Arun Bokde
Author: Patricia Conrod
Author: Herta Flor
Author: Vincent Frouin
Author: Jürgen Gallinat
Author: Hugh Garavan
Author: Penny Gowland
Author: Andreas Heinz
Author: Bernd Ittermann
Author: Mark G. Lathrop
Author: Jean-Luc Martinot
Author: Tomáš Paus
Author: Sylvane Desrivieres
Author: Marcus R. Munafò
Author: Marjo-Riitta Järvelin
Author: Gunter Schumann

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