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Nat Med. 2019 Oct;25(10):1477-1487. doi: 10.1038/s41591-019-0581-5. Epub 2019 Sep 23.

A framework for the investigation of rare genetic disorders in neuropsychiatry.

Author information

1
Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
2
Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
3
Institute for Genomic Medicine, Columbia University Medical Center, Hammer Health Sciences, New York, NY, USA.
4
National Institute of Mental Health, Bethesda, MD, USA.
5
CHU Sainte-Justine Research Centre, University of Montreal, Montreal, Quebec, Canada.
6
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
7
Geisinger Autism & Developmental Medicine Institute, Danville, PA, USA.
8
Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.
9
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
10
Department of Neuroscience, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
11
McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
12
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
13
Center for Autism Research and Treatment, Semel Institute for Neuroscience and Human Behavior and Departments of Neurology and Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
14
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
15
Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA.
16
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
17
Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA, USA.
18
National Center for Advancing Translational Sciences, Bethesda, MD, USA.
19
Department of Psychiatry, Neuropsychiatry Section, and the Lifespan Brain Institute, Perelman School of Medicine and Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA. raquel@pennmedicine.upenn.edu.
20
Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California, Los Angeles, Los Angeles, CA, USA. cbearden@mednet.ucla.edu.

Abstract

De novo and inherited rare genetic disorders (RGDs) are a major cause of human morbidity, frequently involving neuropsychiatric symptoms. Recent advances in genomic technologies and data sharing have revolutionized the identification and diagnosis of RGDs, presenting an opportunity to elucidate the mechanisms underlying neuropsychiatric disorders by investigating the pathophysiology of high-penetrance genetic risk factors. Here we seek out the best path forward for achieving these goals. We think future research will require consistent approaches across multiple RGDs and developmental stages, involving both the characterization of shared neuropsychiatric dimensions in humans and the identification of neurobiological commonalities in model systems. A coordinated and concerted effort across patients, families, researchers, clinicians and institutions, including rapid and broad sharing of data, is now needed to translate these discoveries into urgently needed therapies.

PMID:
31548702
DOI:
10.1038/s41591-019-0581-5

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