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Eur Neuropsychopharmacol. 2018 Oct;28(10):1103-1114. doi: 10.1016/j.euroneuro.2018.07.101. Epub 2018 Aug 11.

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

Author information

1
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Centre for Population Neuroscience and Precision Medicine (PONS), MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
2
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Centre for Population Neuroscience and Precision Medicine (PONS), MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; St George's, University of London, London, United Kingdom.
3
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Centre for Population Neuroscience and Precision Medicine (PONS), MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China.
4
Section of Genomics of Common Disease, Department of Medicine, Imperial College London, London, United Kingdom; Centre for Pharmacology and Therapeutics, Department of Medicine, Imperial College London, London, United Kingdom.
5
Clinical Physics, Barts Health NHS Trust, The Royal London Hospital, London, UK; One Small Step Gait Laboratory, Guy׳s and St. Thomas' NHS Foundation Trust, Guy׳s Hospital, London, UK.
6
UCL Institute of Health Informatics, University College, London, UK.
7
Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy; Università Vita-Salute San Raffaele, Milan 20132, Italy.
8
Intelligent Autonomous Systems Group, Department of Computer Science, Technische Universität Darmstadt, Darmstadt, Germany; Max Planck Institute for Intelligent Systems, Tübingen, Germany.
9
University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, 20246, Hamburg, Germany.
10
Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
11
UCL Great Ormond Street Institute of Child Health, London; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Kingston upon Thames, UK.
12
Division of Diabetes, Endocrinology and Metabolism, Faculty of Medicine, Imperial College London, London, United Kingdom.
13
Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland; Cambridge Cognition Ltd, Cambridge, UK.
14
Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
15
Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
16
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, Canada.
17
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany; Department of Psychology, School of Social Sciences, University of Mannheim, 68131 Mannheim, Germany.
18
NeuroSpin, Bât 145 Gif-sur-Yvette, Paris, France.
19
Clinic for Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
20
Departments of Psychiatry and Psychology, University of Vermont, 05405 Burlington, Vermont, USA.
21
Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, United Kingdom.
22
Clinic for Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
23
Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany.
24
Department of Human Genetics, McGill University, 1205 Dr Penfield Avenue, Montreal, QC, Canada; McGill University, Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, QC, Canada.
25
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud - Paris Saclay, University Paris Descartes; DIGITEO labs, Gif sur Yvette; France.
26
Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital and Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, Canada.
27
MRC Integrative Epidemiology Unit, UK Centre for Tobacco Control Studies and School of Experimental Psychology, University of Bristol, Bristol, United Kingdom.
28
Institute of Health Sciences, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, United Kingdom; Unit of Primary Care, Oulu University Hospital, Oulu, Finland; Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland.
29
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Centre for Population Neuroscience and Precision Medicine (PONS), MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. Electronic address: gunter.schumann@kcl.ac.uk.

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:

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

PMID:
30104163
PMCID:
PMC6525784
DOI:
10.1016/j.euroneuro.2018.07.101
[Indexed for MEDLINE]
Free PMC Article

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