title: Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population.
abstract: Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of this risk are unclear in people not ascertained for neuropsychiatric symptoms. Using several large ASD consortium and population-based resources (total n > 38,000), we find genome-wide genetic links between ASDs and typical variation in social behavior and adaptive functioning. This finding is evidenced through both LD score correlation and de novo variant analysis, indicating that multiple types of genetic risk for ASDs influence a continuum of behavioral and developmental traits, the severe tail of which can result in diagnosis with an ASD or other neuropsychiatric disorder. A continuum model should inform the design and interpretation of studies of neuropsychiatric disease biology.
authors.affiliation: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Elise B
authors.initials: EB
authors.lastname: Robinson
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
authors.forename: Beate
authors.initials: B
authors.lastname: St Pourcain
authors.affiliation: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Verneri
authors.identifier: 0000-0002-0073-4675
authors.initials: V
authors.lastname: Anttila
authors.affiliation: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Kosmicki
authors.affiliation: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Brendan
authors.initials: B
authors.lastname: Bulik-Sullivan
authors.affiliation: Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, Denmark.|Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark.|Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.|Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Grove
authors.affiliation: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Maller
authors.affiliation: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Program in Genetics and Genomics, Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kaitlin E
authors.initials: KE
authors.lastname: Samocha
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Stephan J
authors.identifier: 0000-0001-9112-5148
authors.initials: SJ
authors.lastname: Sanders
authors.affiliation: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Psychiatry and Psychotherapy, Charité, Campus Mitte, Berlin, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ripke
authors.affiliation: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Martin
authors.affiliation: Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Mads V
authors.initials: MV
authors.lastname: Hollegaard
authors.affiliation: Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark.|Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Copenhagen, Denmark.|Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.affiliation: Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: David M
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Benjamin M
authors.identifier: 0000-0003-1513-6077
authors.initials: BM
authors.lastname: Neale
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.affiliation: Behavioural Sciences Unit, Institute of Child Health, University College London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Skuse
authors.affiliation: Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, Denmark.|Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark.|National Centre for Register-based Research, University of Aarhus, Aarhus, Denmark.
authors.forename: Preben Bo
authors.initials: PB
authors.lastname: Mortensen
authors.affiliation: Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, Denmark.|Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark.|Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
authors.forename: Anders D
authors.initials: AD
authors.lastname: Børglum
authors.affiliation: Department of Psychological Sciences, Centre for Brain and Cognitive Development, Birkbeck University of London, London, UK.
authors.forename: Angelica
authors.initials: A
authors.lastname: Ronald
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.affiliation: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Mark J
authors.identifier: 0000-0002-0949-8752
authors.initials: MJ
authors.lastname: Daly
mesh_terms: D000328:Adult; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D002648:Child; D003147:Communication Disorders / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006305:Health Status Indicators; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*