Whole genome sequencing in psychiatric disorders: the WGSPD consortium

Stephan J Sanders; Benjamin M Neale; Hailiang Huang; Donna M Werling; Joon-Yong An; Shan Dong; Whole Genome Sequencing for Psychiatric Disorders (WGSPD); Goncalo Abecasis; P Alexander Arguello; John Blangero; Michael Boehnke; Mark J Daly; Kevin Eggan; Daniel H Geschwind; David C Glahn; David B Goldstein; Raquel E Gur; Robert E Handsaker; Steven A McCarroll; Roel A Ophoff; Aarno Palotie; Carlos N Pato; Chiara Sabatti; Matthew W State; A Jeremy Willsey; Steven E Hyman; Anjene M Addington; Thomas Lehner; Nelson B Freimer

doi:10.1038/s41593-017-0017-9

Whole genome sequencing in psychiatric disorders: the WGSPD consortium

Nat Neurosci. 2017 Dec;20(12):1661-1668. doi: 10.1038/s41593-017-0017-9.

Authors

Stephan J Sanders¹, Benjamin M Neale^{2

3}, Hailiang Huang^{2

3}, Donna M Werling¹, Joon-Yong An¹, Shan Dong¹; Whole Genome Sequencing for Psychiatric Disorders (WGSPD); Goncalo Abecasis⁴, P Alexander Arguello⁵, John Blangero⁶, Michael Boehnke⁴, Mark J Daly^{2

3}, Kevin Eggan³, Daniel H Geschwind^{7

8}, David C Glahn⁹, David B Goldstein¹⁰, Raquel E Gur¹¹, Robert E Handsaker³, Steven A McCarroll³, Roel A Ophoff^{12

13

14}, Aarno Palotie³, Carlos N Pato¹⁵, Chiara Sabatti¹⁶, Matthew W State¹, A Jeremy Willsey¹, Steven E Hyman¹⁷, Anjene M Addington¹⁸, Thomas Lehner¹⁹, Nelson B Freimer²⁰

Affiliations

¹ Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
² Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
³ Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁴ Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
⁵ National Institute of Mental Health, Bethesda, MD, USA.
⁶ South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, School of Medicine, Brownsville, TX, USA.
⁷ Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁸ Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁹ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
¹⁰ Institute for Genomic Medicine, Columbia University Medical Center, Hammer Health Sciences, New York, NY, USA.
¹¹ Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹² Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
¹³ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
¹⁴ Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁵ Department of Psychiatry, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁶ Department of Health Research and Policy, Division of Biostatistics, Stanford University, Stanford, CA, USA.
¹⁷ Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. seh@harvard.edu.
¹⁸ Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA. anjene.addington@nih.gov.
¹⁹ Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA. tlehner@mail.nih.gov.
²⁰ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA. nfreimer@mednet.ucla.edu.

Abstract

As technology advances, whole genome sequencing (WGS) is likely to supersede other genotyping technologies. The rate of this change depends on its relative cost and utility. Variants identified uniquely through WGS may reveal novel biological pathways underlying complex disorders and provide high-resolution insight into when, where, and in which cell type these pathways are affected. Alternatively, cheaper and less computationally intensive approaches may yield equivalent insights. Understanding the role of rare variants in the noncoding gene-regulating genome, through pilot WGS projects, will be critical to determine which of these two extremes best represents reality. With large cohorts, well-defined risk loci, and a compelling need to understand the underlying biology, psychiatric disorders have a role to play in this preliminary WGS assessment. The WGSPD consortium will integrate data for 18,000 individuals with psychiatric disorders, beginning with autism spectrum disorder, schizophrenia, bipolar disorder, and major depressive disorder, along with over 150,000 controls.

Publication types

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

MeSH terms

Biological Psychiatry / trends*
Genetic Variation
Genome, Human
Humans
Mental Disorders / genetics*
Whole Genome Sequencing / trends*

Abstract

Publication types

MeSH terms

Grants and funding