This Accepted Manuscript has not been copyedited and formatted. The final version may differ from this version. Research Articles: Behavioral/Cognitive Overdominant effect of a CHRNA4 polymorphism on cingulo-opercular network activity and cognitive control Sepideh Sadaghiani1,2,3, Bernard Ng1,4, Andre Altmann1,5, Jean-Baptiste Poline6, Tobias Banaschewski7, Arun L.W. Bokde8, Uli Bromberg9, Christian Büchel9, Erin Burke Quinlan10, Patricia Conrod10, Sylvane Desrivières10, Herta Flor11,12, Vincent Frouin13, Hugh Garavan14, Penny Gowland15, Jürgen Gallinat16, Andreas Heinz16, Bernd Ittermann17, Jean-Luc Martinot18, Marie-Laure Paillère Martinot19, Hervé Lemaitre19, Frauke Nees7,11, Dimitri Papadopoulos Orfanos13, Tomáš Paus20, Luise Poustka21,22, Sabina Millenet7, Juliane H. Fröhner23, Michael N. Smolka23, Henrik Walter16, Robert Whelan24, Gunter Schumann10, Valerio Napolioni1 and Michael Greicius1 1Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA 2Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA 3Beckman Institute for Advanced Science and Technology, Urbana, IL 61801, USA 4Department of Statistics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada 5Translational Imaging Group, Centre for Medical Image Computing (CMIC), Department of Medical Physics & Bioengineering, University College London, London WC1E 6BT, United Kingdom 6Department of Psychology, University of California at Berkeley, Berkeley, CA 94720, USA 7Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany 8Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland 9University Medical Centre Hamburg-Eppendorf, 20246, Hamburg, Germany 10Medical Research Council - Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, United Kingdom 11Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany 12Department of Psychology, School of Social Sciences, University of Mannheim, 68131 Mannheim, Germany 13NeuroSpin, CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France 14Departments of Psychiatry and Psychology, University of Vermont, 05405 Burlington, Vermont, USA 15Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, United Kingdom 16Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Berlin, Germany 17Physikalisch-Technische Bundesanstalt (PTB), Berlin, Germany 18Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 “Neuroimaging & Psychiatry”, University Paris Sud — Paris Saclay, University Paris Descartes; Service Hospitalier Frédéric Joliot, Orsay; and Maison de Solenn, Paris, France 19Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 “Neuroimaging & Psychiatry”, University Paris Sud — Paris Saclay, University Paris Descartes; and AP-HP, Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris, France 20Rotman Research Institute, Baycrest and Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, M6A 2E1, Canada 21Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, 37075 Göttingen, Germany 22Clinic for Child and Adolescent Psychiatry, Medical University of Vienna, 1090 Vienna, Austria 23Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany 24School of Psychology and Global Brain Health Institute, Trinity College Dublin, Ireland DOI: 10.1523/JNEUROSCI.0991-17.2017 Accepted manuscripts are peer-reviewed but have not been through the copyediting, formatting, or proofreading process. Copyright © 2017 the authors Received: 12 April 2017 Revised: 20 August 2017 Accepted: 22 August 2017 Published: 6 September 2017 Author contributions: S.S., A.A., V.N., and M.G. designed research; S.S., B.N., A.A., and V.N. performed research; S.S., B.N., A.A., J.-B.P., T.B., A.B., U.B., C.B., E.B.Q., P.C., S.D., H.F., V.F., H.G., P.G., J.G., A.H., B.I., J.-L.M., M.-L.P.M., H.L., F.N., D.P.O., T.P., L.P., S.M., J.F., M.N.S., H.W., R.W., and G.S. contributed unpublished reagents/analytic tools; S.S., B.N., A.A., and V.N. analyzed data; S.S., V.N., and M.G. wrote the paper. Conflict of Interest: The authors declare no competing financial interests. We thank Stephen M. Malone for supporting us in a multi-modal investigation of CHRNA4. This work was supported by funding from The Feldman Family Foundation and The J. W. Bagley Foundation. AA holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship. This work was supported by the Medical Research Council [grant number MR/L016311/1].; The IMAGEN consortium has received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement- related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY' (Brain network based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics) (MR/N027558/1), the FP7 projects IMAGEMEND(602450; IMAging GEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EU-AIMS (115300-2), the Medical Research Council Grant 'c-VEDA' (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/ N000390/1), the Swedish Research Council FORMAS, the Medical Research Council, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc01ZX1311A; Forschungsnetz AERIAL), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-1, SM 80/7-2, SFB 940/1). Further support was provided by grants from: ANR (project AF12- NEUR0008-01 - WM2NA, and ANR-12-SAMA-0004), the Fondation de France, the Fondation pour la Recherche Médicale, the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012; the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), U.S.A. (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1), and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. Corresponding author: Sepideh Sadaghiani, PhD, Assistant Professor, Department of Psychology, Cognitive Neuroscience Division, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Beckman Institute, 405 N Mathews Avenue, Urbana, IL 61801, [email protected], https://connectlab.beckman.illinois.edu Cite as: J. Neurosci ; 10.1523/JNEUROSCI.0991-17.2017 Alerts: Sign up at www.jneurosci.org/cgi/alerts to receive customized email alerts when the fully formatted version of this article is published. 1 Overdominant effect of a CHRNA4 polymorphism 2 on cingulo-opercular network activity and cognitive control 3 Abbreviated Title: Neuroimaging genetics of CHRNA4 4 Sepideh Sadaghiani* 1,2,3, Bernard Ng1,4, Andre Altmann1,5, Jean-Baptiste Poline6, Tobias 5 Banaschewski7; Arun L.W. Bokde8; Uli Bromberg9; Christian Büchel9; Erin Burke Quinlan10; 6 Patricia Conrod10; Sylvane Desrivières10; Herta Flor11,12; Vincent Frouin13; Hugh Garavan14; 7 Penny Gowland15; Jürgen Gallinat16, Andreas Heinz16; Bernd Ittermann17; Jean-Luc Martinot18, 8 Marie-Laure Paillère Martinot19; Hervé Lemaitre19; Frauke Nees7,11; Dimitri Papadopoulos 9 Orfanos13; Tomáš Paus20; Luise Poustka21,22, Sabina Millenet7; Juliane H. Fröhner23; Michael N. 10 Smolka23; Henrik Walter16; Robert Whelan24; Gunter Schumann10, Valerio Napolioni1, Michael 11 Greicius1 12 13 1 Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA 14 2 Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA 15 3 Beckman Institute for Advanced Science and Technology, Urbana, IL 61801, USA 16 4 Department of Statistics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada 17 5 Translational Imaging Group, Centre for Medical Image Computing (CMIC), Department of Medical 18 Physics & Bioengineering, University College London, London WC1E 6BT, United Kingdom 19 6 Department of Psychology, University of California at Berkeley, Berkeley, CA 94720, USA 20 7 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, 21 Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany; 22 8 Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College 23 Dublin, Dublin, Ireland; 24 9 University Medical Centre Hamburg-Eppendorf, 20246, Hamburg, Germany; 25 10Medical Research Council - Social, Genetic and Developmental Psychiatry