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

C Macare, F Ducci, Y Zhang, B Ruggeri, T Jia, M Kaakinen, G Kalsi, P Charoen, F Casoni, J Peters, U Bromberg, M Hill, J Buxton, A Blakemore, J Veijola, C Büchel, T Banaschewski, ALW Bokde, P Conrod, H FlorV Frouin, J Gallinat, H Garavan, PA Gowland, A Heinz, B Ittermann, M Lathrop, JL Martinot, T Paus, S Desrivières, M Munafò, MR Järvelin, G Schumann, The IMAGEN Consortium

Research output: Contribution to journalArticle

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. © 2018
Original languageEnglish
Pages (from-to)1103-1114
Number of pages12
JournalEuropean Neuropsychopharmacology
Volume28
Issue number10
DOIs
Publication statusPublished - 2018

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Reward
Smoking
Multigene Family
Alleles
Gene Expression
Corpus Striatum
Cotinine
Adolescent Behavior
Individuality
Meta-Analysis
Oxygen
Genes

Cite this

Macare, C., Ducci, F., Zhang, Y., Ruggeri, B., Jia, T., Kaakinen, M., ... Consortium, T. IMAGEN. (2018). A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response. European Neuropsychopharmacology, 28(10), 1103-1114. https://doi.org/10.1016/j.euroneuro.2018.07.101

A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response. / 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; Consortium, The IMAGEN.

In: European Neuropsychopharmacology, Vol. 28, No. 10, 2018, p. 1103-1114.

Research output: Contribution to journalArticle

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 & Consortium, TIMAGEN 2018, 'A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response', European Neuropsychopharmacology, vol. 28, no. 10, pp. 1103-1114. https://doi.org/10.1016/j.euroneuro.2018.07.101
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 ; Consortium, The IMAGEN. / A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response. In: European Neuropsychopharmacology. 2018 ; Vol. 28, No. 10. pp. 1103-1114.
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AU - Ducci, F

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AU - Jia, T

AU - Kaakinen, M

AU - Kalsi, G

AU - Charoen, P

AU - Casoni, F

AU - Peters, J

AU - Bromberg, U

AU - Hill, M

AU - Buxton, J

AU - Blakemore, A

AU - Veijola, J

AU - Büchel, C

AU - Banaschewski, T

AU - Bokde, ALW

AU - Conrod, P

AU - Flor, H

AU - Frouin, V

AU - Gallinat, J

AU - Garavan, H

AU - Gowland, PA

AU - Heinz, A

AU - Ittermann, B

AU - Lathrop, M

AU - Martinot, JL

AU - Paus, T

AU - Desrivières, S

AU - Munafò, M

AU - Järvelin, MR

AU - Schumann, G

AU - Consortium, The IMAGEN

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N2 - 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. © 2018

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