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

The IMAGEN Consortium

doi:10.1016/j.euroneuro.2018.07.101

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

The IMAGEN Consortium

Vice Chancellor's Office

King's College London
MRC Laboratory
St George's University Hospitals NHS Foundation Trust
Fudan University
Imperial College London
Barts Health NHS Trust
Guy's and St. Thomas' Hospitals NHS Foundation Trust
University College London
San Raffaele Scientific Institute
Università Vita-Salute San Raffaele
Technische Universität Darmstadt
Max Planck Institute for Intelligent Systems
University Medical Centre Hamburg-Eppendorf
Cardiff University
Kingston University
University of Oulu
Cambridge Cognition Ltd
Universität Heidelberg
Trinity College Dublin
Sainte-Justine Hospital
University of Mannheim
Institut National de Recherche en Informatique et en Automatique (INRIA) Parietal
University of Vermont
University of Nottingham
Charité – Universitätsmedizin Berlin
Physikalisch-Technische Bundesanstalt
McGill University
Institut National de la Sante et de la Recherche Medicale (INSERM)
DIGITEO Labs
Bloorview Research Institute
University of Bristol
Oulu University Hospital
National Institute for Health and Welfare (THL)

Research output: Contribution to journal › Article › peer-review

20 Citations (SciVal)

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.

Original language	English
Pages (from-to)	1103-1114
Number of pages	12
Journal	European Neuropsychopharmacology
Volume	28
Issue number	10
Early online date	11 Aug 2018
DOIs	https://doi.org/10.1016/j.euroneuro.2018.07.101
Publication status	Published - 31 Oct 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

fMRI
Genetics
IMAGEN-ALSPAC-NFBC
Meta-analysis
Risk taking
Smoking

ASJC Scopus subject areas

Pharmacology
Neurology
Clinical Neurology
Psychiatry and Mental health
Biological Psychiatry
Pharmacology (medical)

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10.1016/j.euroneuro.2018.07.101Licence: CC BY

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

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.",

keywords = "fMRI, Genetics, IMAGEN-ALSPAC-NFBC, Meta-analysis, Risk taking, Smoking",

author = "\{The IMAGEN Consortium\} and Christine Macare and Francesca Ducci and Yuning Zhang and Barbara Ruggeri and Tianye Jia and Marika Kaakinen and Gursharan Kalsi and Pimphen Charoen and Filippo Casoni and Jan Peters and Uli Bromberg and Matthew Hill and Jessica Buxton and Alexandra Blakemore and Juha Veijola and Christian B{\"u}chel and Tobias Banaschewski and Bokde, \{Arun L.W.\} and Patricia Conrod and Herta Flor and Vincent Frouin and J{\"u}rgen Gallinat and Hugh Garavan and Gowland, \{Penny A.\} and Andreas Heinz and Bernd Ittermann and Mark Lathrop and Martinot, \{Jean Luc\} and Tom{\'a}{\v s} Paus and Sylvane Desrivi{\`e}res and Marcus Munaf{\`o} and J{\"a}rvelin, \{Marjo Riitta\} and Gunter Schumann",

year = "2018",

month = oct,

day = "31",

doi = "10.1016/j.euroneuro.2018.07.101",

language = "English",

volume = "28",

pages = "1103--1114",

journal = "European Neuropsychopharmacology",

issn = "0924-977X",

publisher = "Elsevier B.V.",

number = "10",

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TY - JOUR

T1 - A neurobiological pathway to smoking in adolescence

T2 - TTC12-ANKK1-DRD2 variants and reward response

AU - The IMAGEN Consortium

AU - Macare, Christine

AU - Ducci, Francesca

AU - Zhang, Yuning

AU - Ruggeri, Barbara

AU - Jia, Tianye

AU - Kaakinen, Marika

AU - Kalsi, Gursharan

AU - Charoen, Pimphen

AU - Casoni, Filippo

AU - Peters, Jan

AU - Bromberg, Uli

AU - Hill, Matthew

AU - Buxton, Jessica

AU - Blakemore, Alexandra

AU - Veijola, Juha

AU - Büchel, Christian

AU - Banaschewski, Tobias

AU - Bokde, Arun L.W.

AU - Conrod, Patricia

AU - Flor, Herta

AU - Frouin, Vincent

AU - Gallinat, Jürgen

AU - Garavan, Hugh

AU - Gowland, Penny A.

AU - Heinz, Andreas

AU - Ittermann, Bernd

AU - Lathrop, Mark

AU - Martinot, Jean Luc

AU - Paus, Tomáš

AU - Desrivières, Sylvane

AU - Munafò, Marcus

AU - Järvelin, Marjo Riitta

AU - Schumann, Gunter

PY - 2018/10/31

Y1 - 2018/10/31

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.

AB - 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.

KW - fMRI

KW - Genetics

KW - IMAGEN-ALSPAC-NFBC

KW - Meta-analysis

KW - Risk taking

KW - Smoking

UR - https://www.scopus.com/pages/publications/85051403107

U2 - 10.1016/j.euroneuro.2018.07.101

DO - 10.1016/j.euroneuro.2018.07.101

M3 - Article

C2 - 30104163

AN - SCOPUS:85051403107

SN - 0924-977X

VL - 28

SP - 1103

EP - 1114

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

IS - 10

ER -

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

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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