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Title: A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response
Authors: Macare, C
Ducci, F
Zhang, Y
Ruggeri, B
Jia, T
Kaakinen, M
Kalsi, G
Charoen, P
Casoni, F
Peters, J
Bromberg, U
Hill, M
Buxton, J
Blakemore, A
Veijola, J
Büchel, C
Banaschewski, T
Bokde, ALW
Conrod, P
Flor, H
Frouin, V
Gallinat, J
Garavan, H
Gowland, PA
Heinz, A
Ittermann, B
Lathrop, M
Martinot, JL
Paus, T
Desrivières, S
Munafò, M
Järvelin, MR
Schumann, G
Keywords: fMRI;Genetics;IMAGEN-ALSPAC-NFBC;Meta-analysis;Risk taking;Smoking
Issue Date: 11-Aug-2018
Publisher: Elsevier
Citation: European Neuropsychopharmacology, 2018
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.
ISSN: 0924-977X
Appears in Collections:Dept of Life Sciences Research Papers

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