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

Elise B Robinson; Beate St Pourcain; Verneri Anttila; Jack A Kosmicki; Brendan Bulik-Sullivan; Jakob Grove; Julian Maller; Kaitlin E Samocha; Stephan J Sanders; Stephan Ripke; Joanna Martin; Mads V Hollegaard; Thomas Werge; David M Hougaard; iPSYCH-SSI-Broad Autism Group; Benjamin M Neale; David M Evans; David Skuse; Preben Bo Mortensen; Anders D Børglum; Angelica Ronald; George Davey Smith; Mark J Daly

doi:10.1038/ng.3529

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

Nat Genet. 2016 May;48(5):552-5. doi: 10.1038/ng.3529. Epub 2016 Mar 21.

Authors

Elise B Robinson^{1

2

3}, Beate St Pourcain^{4

5}, Verneri Anttila^{1

2

3}, Jack A Kosmicki^{1

2

3

6}, Brendan Bulik-Sullivan^{1

2

3}, Jakob Grove^{7

8

9

10}, Julian Maller^{1

2

3}, Kaitlin E Samocha^{1

2

3

11}, Stephan J Sanders¹², Stephan Ripke^{1

2

3

13}, Joanna Martin^{1

2

3}, Mads V Hollegaard¹⁴, Thomas Werge^{8

15

16}, David M Hougaard¹⁴; iPSYCH-SSI-Broad Autism Group; Benjamin M Neale^{1

2

3

17}, David M Evans^{4

18}, David Skuse¹⁹, Preben Bo Mortensen^{7

8

20}, Anders D Børglum^{7

8

9}, Angelica Ronald²¹, George Davey Smith⁴, Mark J Daly^{1

2

3}

Collaborators

Affiliations

¹ Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
² Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
³ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
⁴ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁵ Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
⁶ Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.
⁷ Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, Denmark.
⁸ Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark.
⁹ Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
¹⁰ Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
¹¹ Program in Genetics and Genomics, Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA.
¹² Department of Psychiatry, University of California, San Francisco, San Francisco, California, USA.
¹³ Department of Psychiatry and Psychotherapy, Charité, Campus Mitte, Berlin, Germany.
¹⁴ Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
¹⁵ Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Copenhagen, Denmark.
¹⁶ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁷ Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
¹⁸ Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
¹⁹ Behavioural Sciences Unit, Institute of Child Health, University College London, London, UK.
²⁰ National Centre for Register-based Research, University of Aarhus, Aarhus, Denmark.
²¹ Department of Psychological Sciences, Centre for Brain and Cognitive Development, Birkbeck University of London, London, UK.

PMID: 26998691
PMCID: PMC4986048
DOI: 10.1038/ng.3529

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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*

Abstract

Publication types

MeSH terms

Grants and funding