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

Macare, Christine, Ducci, Francesca, Zhang, Yuning, Ruggeri, Barbara, Jia, Tianye, Kaakinen, Marika, Kalsi, Gursharan, Charoen, Pimphen, Casoni, Filippo, Peters, Jan, Bromberg, Uli, Hill, Matthew ORCID: https://orcid.org/0000-0001-6776-8709, Buxton, Jessica, Blakemore, Alexandra, Veijola, Juha, Büchel, Christian, Banaschewski, Tobias, Bokde, Arun L.W., Conrod, Patricia, Flor, Herta, Frouin, Vincent, Gallinat, Jürgen, Garavan, Hugh, Gowland, Penny A., Heinz, Andreas, Ittermann, Bernd, Lathrop, Mark, Martinot, Jean-Luc, Paus, Tomá?, Desrivières, Sylvane, Munafò, Marcus, Järvelin, Marjo-Riitta and Schumann, Gunter 2018. A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response. European Neuropsychopharmacology 28 (10) 10.1016/j.euroneuro.2018.07.101

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Elsevier
ISSN:	0924-977X
Date of First Compliant Deposit:	26 September 2018
Date of Acceptance:	17 July 2018
Last Modified:	14 Nov 2024 11:45
URI:	https://orca.cardiff.ac.uk/id/eprint/115252

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