title: Converging genetic and functional brain imaging evidence links neuronal excitability to working memory, psychiatric disease, and brain activity.
abstract: Working memory, the capacity of actively maintaining task-relevant information during a cognitive task, is a heritable trait. Working memory deficits are characteristic for many psychiatric disorders. We performed genome-wide gene set enrichment analyses in multiple independent data sets of young and aged cognitively healthy subjects (n = 2,824) and in a large schizophrenia case-control sample (n = 32,143). The voltage-gated cation channel activity gene set, consisting of genes related to neuronal excitability, was robustly linked to performance in working memory-related tasks across ages and to schizophrenia. Functional brain imaging in 707 healthy participants linked this gene set also to working memory-related activity in the parietal cortex and the cerebellum. Gene set analyses may help to dissect the molecular underpinnings of cognitive dimensions, brain activity, and psychopathology.
authors: Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Psychiatric University Clinics, University of Basel, CH-4055 Basel, Switzerland. Electronic address: angela.heck@unibas.ch.
authors: Angela
authors: A
authors: Heck
authors: Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Division of Cognitive Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland.
authors: Matthias
authors: M
authors: Fastenrath
authors: Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland.
authors: Sandra
authors: S
authors: Ackermann
authors: Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland.
authors: Bianca
authors: B
authors: Auschra
authors: Department of Psychiatry, Technical University of Munich, 85748 Munich, Germany.
authors: Horst
authors: H
authors: Bickel
authors: Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Division of Cognitive Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland.
authors: David
authors: D
authors: Coynel
authors: Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Division of Cognitive Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland.
authors: Leo
authors: L
authors: Gschwind
authors: Department of Psychiatry, University of Bonn, 53105 Bonn, Germany; DZNE, German Center for Neurogenerative Diseases, 53105 Bonn, Germany.
authors: Frank
authors: F
authors: Jessen
authors: Department of Primary Medical Care, Center of Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors: Hanna
authors: H
authors: Kaduszkiewicz
authors: Department of Psychiatry, University of Bonn, 53105 Bonn, Germany; DZNE, German Center for Neurogenerative Diseases, 53105 Bonn, Germany.
authors: Wolfgang
authors: W
authors: Maier
authors: Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Psychiatric University Clinics, University of Basel, CH-4055 Basel, Switzerland.
authors: Annette
authors: A
authors: Milnik
authors: Institute of General Practice, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
authors: Michael
authors: M
authors: Pentzek
authors: Institute of Social Medicine, Occupational Health and Public Health, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
authors: Steffi G
authors: SG
authors: Riedel-Heller
authors: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
authors: Stephan
authors: S
authors: Ripke
authors: Division of Cognitive Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland.
authors: Klara
authors: K
authors: Spalek
authors: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264, USA.
authors: Patrick
authors: P
authors: Sullivan
authors: Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Psychiatric University Clinics, University of Basel, CH-4055 Basel, Switzerland.
authors: Christian
authors: C
authors: Vogler
authors: Department of Psychiatry, University of Bonn, 53105 Bonn, Germany; DZNE, German Center for Neurogenerative Diseases, 53105 Bonn, Germany.
authors: Michael
authors: M
authors: Wagner
authors: Central Institute of Mental Health, 68159 Mannheim, Germany.
authors: Siegfried
authors: S
authors: Weyerer
authors: Department of Psychiatry, University of Bonn, 53105 Bonn, Germany; DZNE, German Center for Neurogenerative Diseases, 53105 Bonn, Germany.
authors: Steffen
authors: S
authors: Wolfsgruber
authors: Psychiatric University Clinics, University of Basel, CH-4055 Basel, Switzerland; Division of Cognitive Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Transfaculty Research Platform, University of Basel, CH-4012 Basel, Switzerland.
authors: Dominique J-F
authors: DJ
authors: de Quervain
authors: Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Psychiatric University Clinics, University of Basel, CH-4055 Basel, Switzerland; Department Biozentrum, Life Sciences Training Facility, University of Basel, CH-4056 Basel, Switzerland; Transfaculty Research Platform, University of Basel, CH-4012 Basel, Switzerland. Electronic address: andreas.papas@unibas.ch.
authors: Andreas
authors: A
authors: Papassotiropoulos
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001921:Brain / Q000502:physiology; D015220:Calcium Channels / Q000235:genetics* / Q000502:physiology*; D016022:Case-Control Studies; D002531:Cerebellum / Q000502:physiology; D003071:Cognition / Q000502:physiology; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D010296:Parietal Lobe / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D015220:Calcium Channels