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PMID: 26998691 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population.

Nature genetics ·Vol. 48 ·No. 5 ·2016-00-00 ·Pages 552-5

Robinson EB, St Pourcain B, Anttila V, Kosmicki JA, Bulik-Sullivan B, Grove J, Maller J, Samocha KE, Sanders SJ, Ripke S, Martin J, Hollegaard MV, Werge T, Hougaard DM, iPSYCH-SSI-Broad Autism Group, Neale BM, Evans DM, Skuse D, Mortensen PB, Børglum AD, Ronald A, Smith GD, Daly MJ

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.

MeSH Terms
Adult Autism Spectrum Disorder/genetics Child Communication Disorders/genetics Female Genetic Predisposition to Disease Genetic Variation Genetics, Population Genome-Wide Association Study Health Status Indicators Humans Male Mental Disorders/genetics
Authors & Affiliations
23 authors, click to expand affiliations / ORCID
Robinson Elise B
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.
St Pourcain Beate
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK. | Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
Anttila Verneri ORCID
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.
Kosmicki Jack A
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.
Bulik-Sullivan Brendan
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.
Grove Jakob
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.
Maller Julian
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.
Samocha Kaitlin E
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.
Sanders Stephan J ORCID
Department of Psychiatry, University of California, San Francisco, San Francisco, California, USA.
Ripke Stephan
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.
Martin Joanna
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.
Hollegaard Mads V
Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Werge Thomas
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.
Hougaard David M
Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
iPSYCH-SSI-Broad Autism Group
Neale Benjamin M ORCID
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.
Evans David M
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK. | Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
Skuse David
Behavioural Sciences Unit, Institute of Child Health, University College London, London, UK.
Mortensen Preben Bo
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.
Børglum Anders D
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.
Ronald Angelica
Department of Psychological Sciences, Centre for Brain and Cognitive Development, Birkbeck University of London, London, UK.
Smith George Davey
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Daly Mark J ORCID
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.
Investigators
20 investigators, click to expand
Als Thomas D
Baekvad-Hansen Marie
Belliveau Richard
Demontis Ditte
Dumont Ashley
Goldstein Jacqueline
Grauholm Jonas
Hansen Christine S
Hansen Thomas F
Howrigan Daniel
Lescai Francesco
Mattheisen Manuel
Moran Jennifer
Mors Ole
Nordentoft Merete
Norgaard-Pedersen Bent
Poterba Timothy
Poulsen Jesper
Stevens Christine
Walters Raymond
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.3529
Published
2016-00-00
Epub
2016-00-21
Pages
552-5
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC4986048
Subset
IM
Grants
NIMH NIH HHS · K01 MH099286 · United States
Wellcome Trust · 102215 · United Kingdom
Medical Research Council · MC_PC_15018 · United Kingdom
Medical Research Council · MC_UU_12013/1 · United Kingdom
Medical Research Council · MC_UU_12013/4 · United Kingdom
NIMH NIH HHS · U01 MH094432 · United States
Medical Research Council · G9815508 · United Kingdom
Corrections
CommentIn
PMID: 27659318
External Links
PubMed source DOI: 10.1038/ng.3529 PMC Full Text View journal details
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