title: Genetic basis of a cognitive complexity metric.
abstract: Relational complexity (RC) is a metric reflecting capacity limitation in relational processing. It plays a crucial role in higher cognitive processes and is an endophenotype for several disorders. However, the genetic underpinnings of complex relational processing have not been investigated. Using the classical twin model, we estimated the heritability of RC and genetic overlap with intelligence (IQ), reasoning, and working memory in a twin and sibling sample aged 15-29 years (N = 787). Further, in an exploratory search for genetic loci contributing to RC, we examined associated genetic markers and genes in our Discovery sample and selected loci for replication in four independent samples (ALSPAC, LBC1936, NTR, NCNG), followed by meta-analysis (N>6500) at the single marker level. Twin modelling showed RC is highly heritable (67%), has considerable genetic overlap with IQ (59%), and is a major component of genetic covariation between reasoning and working memory (72%). At the molecular level, we found preliminary support for four single-marker loci (one in the gene DGKB), and at a gene-based level for the NPS gene, having influence on cognition. These results indicate that genetic sources influencing relational processing are a key component of the genetic architecture of broader cognitive abilities. Further, they suggest a genetic cascade, whereby genetic factors influencing capacity limitation in relational processing have a flow-on effect to more complex cognitive traits, including reasoning and working memory, and ultimately, IQ.
authors: Neuroimaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Narelle K
authors: NK
authors: Hansell
authors: School of Applied Psychology, Griffith University, Mt Gravatt Campus, Brisbane, Australia; Behavioural Basis of Health Program, Griffith Health Institute and School of Applied Psychology, Griffith University, Brisbane, Australia.
authors: Graeme S
authors: GS
authors: Halford
authors: School of Applied Psychology, Griffith University, Gold Coast Campus, Southport, Australia; Behavioural Basis of Health Program, Griffith Health Institute and School of Applied Psychology, Griffith University, Brisbane, Australia.
authors: Glenda
authors: G
authors: Andrews
authors: Behavioural Basis of Health Program, Griffith Health Institute and School of Applied Psychology, Griffith University, Brisbane, Australia.
authors: David H K
authors: DH
authors: Shum
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom; Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors: Sarah E
authors: SE
authors: Harris
authors: Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
authors: Gail
authors: G
authors: Davies
authors: Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
authors: Sanja
authors: S
authors: Franic
authors: K.G. Jebsen Centre for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway; Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors: Andrea
authors: A
authors: Christoforou
authors: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Psychology, University of Queensland, St Lucia, Brisbane, Australia.
authors: Brendan
authors: B
authors: Zietsch
authors: Molecular Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Jodie
authors: J
authors: Painter
authors: Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Sarah E
authors: SE
authors: Medland
authors: Avera Institute for Human Genetics, Avera McKennan Hospital & University Health Center, Sioux Falls, South Dakota, United States of America.
authors: Erik A
authors: EA
authors: Ehli
authors: Avera Institute for Human Genetics, Avera McKennan Hospital & University Health Center, Sioux Falls, South Dakota, United States of America.
authors: Gareth E
authors: GE
authors: Davies
authors: K.G. Jebsen Centre for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway; Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors: Vidar M
authors: VM
authors: Steen
authors: K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway; Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway; Center for Research on Aging and Dementia, Haraldsplass Deaconess Hospital, Bergen, Norway.
authors: Astri J
authors: AJ
authors: Lundervold
authors: Department of Psychology, University of Oslo, Oslo, Norway.
authors: Ivar
authors: I
authors: Reinvang
authors: Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Grant W
authors: GW
authors: Montgomery
authors: Department of Psychology, University of Oslo, Oslo, Norway; Norwegian Center for Mental Disorders Research (NORMENT) and the K.G. Jebsen Center for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors: Thomas
authors: T
authors: Espeseth
authors: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Hilleke E
authors: HE
authors: Hulshoff Pol
authors: Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, United Kingdom.
authors: John M
authors: JM
authors: Starr
authors: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Nicholas G
authors: NG
authors: Martin
authors: K.G. Jebsen Centre for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway; Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors: Stephanie
authors: S
authors: Le Hellard
authors: Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
authors: Dorret I
authors: DI
authors: Boomsma
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom; Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors: Ian J
authors: IJ
authors: Deary
authors: Neuroimaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Margaret J
authors: MJ
authors: Wright
mesh_terms: D000293:Adolescent; D000328:Adult; D003071:Cognition; D005260:Female; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D014427:Twins; D055815:Young Adult