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.
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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October 2018
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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