title: ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties.
abstract: Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.|Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: St Pourcain
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Stanley Center for Psychiatric Research and Medical and the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Robinson
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Stanley Center for Psychiatric Research and Medical and the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Anttila
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Stanley Center for Psychiatric Research and Medical and the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Sullivan
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Maller
authors.affiliation: Centre for Child and Adolescent Health, University of Bristol, Bristol, UK.
authors.forename: J
authors.initials: J
authors.lastname: Golding
authors.affiliation: Behavioural and Brain Sciences, Institute of Child Health, University College London, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Skuse
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: S
authors.initials: S
authors.lastname: Ring
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: D M
authors.initials: DM
authors.lastname: Evans
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: S
authors.initials: S
authors.lastname: Zammit
authors.affiliation: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
authors.forename: S E
authors.initials: SE
authors.lastname: Fisher
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Stanley Center for Psychiatric Research and Medical and the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Neale
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: R J L
authors.initials: RJL
authors.lastname: Anney
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Stanley Center for Psychiatric Research and Medical and the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ripke
authors.affiliation: Statens Serum Institut, Department of Congenital Disorders, Copenhagen, Denmark.
authors.forename: M V
authors.initials: MV
authors.lastname: Hollegaard
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.|Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Copenhagen, Denmark.|Institute of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Werge
authors.affiliation: Department of Psychological Sciences, Birkbeck, University of London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Ronald
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.|Department of Biomedicine, Aarhus University, Aarhus, Denmark.|Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.|Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Grove
authors.affiliation: Statens Serum Institut, Department of Congenital Disorders, Copenhagen, Denmark.
authors.forename: D M
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.|Department of Biomedicine, Aarhus University, Aarhus, Denmark.|Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
authors.forename: A D
authors.initials: AD
authors.lastname: Børglum
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.|Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.|National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.
authors.forename: P B
authors.initials: PB
authors.lastname: Mortensen
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Stanley Center for Psychiatric Research and Medical and the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Daly
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: G
authors.initials: G
authors.lastname: Davey Smith
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics; D003142:Communication; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007802:Language; D008137:Longitudinal Studies; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D012919:Social Behavior; D014705:Verbal Behavior / Q000502:physiology*