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Nat Neurosci. 2019 Dec;22(12):1961-1965. doi: 10.1038/s41593-019-0527-8. Epub 2019 Nov 25.

Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants.

Satterstrom FK1,2,3, Walters RK4,5,6, Singh T4,5,6, Wigdor EM4,5,6, Lescai F7,8,9, Demontis D7,8,9, Kosmicki JA4,5,6, Grove J7,8,9,10, Stevens C4, Bybjerg-Grauholm J7,11, Bækvad-Hansen M7,11, Palmer DS4,5,6, Maller JB4,5,6; iPSYCH-Broad Consortium, Nordentoft M7,12, Mors O7,13, Robinson EB4,5,6,14, Hougaard DM7,11, Werge TM7,15,16, Bo Mortensen P7,8,17,18, Neale BM4,5,6,19, Børglum AD20,21,22, Daly MJ23,24,25,26,27.

Author information

1
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. satterst@broadinstitute.org.
2
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. satterst@broadinstitute.org.
3
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. satterst@broadinstitute.org.
4
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
5
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
6
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
7
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
8
iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
9
Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, Denmark.
10
Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
11
Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
12
Mental Health Services in the Capital Region of Denmark, Mental Health Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark.
13
Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
14
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
15
Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
16
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
17
National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.
18
Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
19
Department of Medicine, Harvard Medical School, Boston, MA, USA.
20
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark. anders@biomed.au.dk.
21
iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark. anders@biomed.au.dk.
22
Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, Denmark. anders@biomed.au.dk.
23
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. mjdaly@atgu.mgh.harvard.edu.
24
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. mjdaly@atgu.mgh.harvard.edu.
25
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. mjdaly@atgu.mgh.harvard.edu.
26
Department of Medicine, Harvard Medical School, Boston, MA, USA. mjdaly@atgu.mgh.harvard.edu.
27
Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland. mjdaly@atgu.mgh.harvard.edu.

Abstract

The exome sequences of approximately 8,000 children with autism spectrum disorder (ASD) and/or attention deficit hyperactivity disorder (ADHD) and 5,000 controls were analyzed, finding that individuals with ASD and individuals with ADHD had a similar burden of rare protein-truncating variants in evolutionarily constrained genes, both significantly higher than controls. This motivated a combined analysis across ASD and ADHD, identifying microtubule-associated protein 1A (MAP1A) as a new exome-wide significant gene conferring risk for childhood psychiatric disorders.

PMID:
31768057
PMCID:
PMC6884695
[Available on 2020-05-25]
DOI:
10.1038/s41593-019-0527-8

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