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

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

Eur Neuropsychopharmacol. 2018 10;28(10):1103-1114

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, IMAGEN Consortium

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.

PMID: 30104163 [PubMed – indexed for MEDLINE]