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Psychiatric Genomics: An Update and an Agenda

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Sullivan, Patrick F., Agrawal, Arpana, Bulik, Cynthia M., Andreassen, Ole A., Børglum, Anders D., Breen, Gerome, Cichon, Sven, Edenberg, Howard J. +7 more·2018·American Journal of Psychiatry
DOI 10.1176/appi.ajp.2017.17030283PMC PMC5756100

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Abstract

The Psychiatric Genomics Consortium (PGC) is the largest consortium in the history of psychiatry. This global effort is dedicated to rapid progress and open science, and in the past decade it has delivered an increasing flow of new knowledge about the fundamental basis of common psychiatric disorders. The PGC has recently commenced a program of research designed to deliver "actionable" findings-genomic results that 1) reveal fundamental biology, 2) inform clinical practice, and 3) deliver new therapeutic targets. The central idea of the PGC is to convert the family history risk factor into biologically, clinically, and therapeutically meaningful insights. The emerging findings suggest that we are entering a phase of accelerated genetic discovery for multiple psychiatric disorders. These findings are likely to elucidate the genetic portions of these truly complex traits, and this knowledge can then be mined for its relevance for improved therapeutics and its impact on psychiatric practice within a precision medicine framework. [AJP at 175: Remembering Our Past As We Envision Our Future November 1946: The Genetic Theory of Schizophrenia Franz Kallmann's influential twin study of schizophrenia in 691 twin pairs was the largest in the field for nearly four decades. (Am J Psychiatry 1946; 103:309-322 )].

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  • GWAS of SCZ, BIP, MD, and ADHD from the PGC and other groups have produced many risk loci.

    “Many risk loci have emerged from genome-wide association studies (GWAS) of, amongothers, schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), and attention-deficit/hyperactivity disorder (ADHD) from the Psychiatric Genomics Consortium (PGC) and other efforts”

    From Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders (2019) · cites this paper as Sullivan et al., 2018

  • Psychiatric disorders are highly polygenic, and common variation accounts for a large share of their heritability.

    “Psychiatric disorders are highly polygenic, with a large proportion of heritability contributed by common variation.”

    From Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders (2019) · cites this paper as Sullivan et al., 2018

  • The past decade has seen remarkable progress in elucidating the genetic underpinnings of psychiatric disorders, with numerous findings meeting modern criteria for significance and reproducibility.

    “Despite these challenges, there has been remarkable progress in the past decade in elucidating the genetic underpinnings of psychiatric disorders with numerous findings that meet modern criteria for significance and reproducibility (Geschwind and Flint, 2015; Sullivan et al., 2018).”

    From Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders (2019) · cites this paper as Sullivan et al., 2018

  • The number of cases is the crucial determinant of the number of loci discovered; increasing sample sizes will identify more loci.

    “The crucial determinant of the number of loci discovered is the number of cases; as sample sizes increase, more loci will be identified (Geschwind and Flint, 2015; Sullivan et al., 2018).”

    From Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders (2019) · cites this paper as Sullivan et al., 2018

  • Results to date indicate that psychiatric disorder risk is imparted by many common variants of individually small effects, and several disorders also have contributions from rarer variants with larger impact on risk.

    “The results to date indicate that psychiatric disorder risk is imparted by many common variants of individually small effects, and several disorders also have contributions from rarer variants with larger impact on risk (Geschwind and Flint, 2015; Sullivan et al., 2018).”

    From Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders (2019) · cites this paper as Sullivan et al., 2018

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Authors
Sullivan, P. F., Agrawal, A., Bulik, C. M., Andreassen, O. A., Børglum, A. D., Breen, G., Cichon, S., Edenberg, H. J., Faraone, S. V., Gelernter, J., Mathews, C. A., Nievergelt, C. M., Smoller, J. W., O’Donovan, M. C., & for the Psychiatric Genomics Consortium
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • From the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Departments of Genetics, Psychiatry, and Nutrition, University of North Carolina, Chapel Hill, N.C.; the Department of Psychiatry, Washington University School of Medicine, St Louis; the Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Oslo and Oslo University Hospital, Oslo; the Lundbeck Foundation Initiative for...
  • Broad Institute (US)
Corresponding author
Sullivan, Patrick F.
ORCID
Venue
American Journal of Psychiatry
Publisher
American Psychiatric Association Publishing
Published
2018-01-01
Volume
175
Issue
1
Pages
15-27
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
DOI
10.1176/appi.ajp.2017.17030283
PMC
PMC5756100
OpenAlex
W2609984900
Cited by
676
References
18
Citations by year
2026: 31 · 2025: 46 · 2024: 70 · 2023: 76 · 2022: 78 · 2021: 68 · 2020: 127 · 2019: 101 · 2018: 64 · 2017: 14
FWCI
10.73
Type
journal article
Language
en
Open access
Locations
  • American Journal of Psychiatry (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • JuSER (Forschungszentrum Jülich) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • Purdue University Indianapolis (Indiana University) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • UNC Libraries
Funders
  • Broad Institute
  • Cohen Veterans Bioscience
  • European Commission (HORIZON2020, 667302, 602805)
  • Science Foundation Ireland
  • Lundbeckfonden (R155-2014-1724, R248‐2017‐2003, U01 MH109528)
  • Universitetet i Bergen
  • H. Lundbeck A/S
  • Gillings School of Public Health
  • Stanley Center for Psychiatric Research, Broad Institute
  • Medical Research Council (MR/P005748/1, MR/L010305/1)
  • National Institute of Mental Health (U01MH109514, MH094421, U01MH109528, U01MH085520, U01MH109536, MH109532, U01MH094421, MH109528, R01MH101519, MH085520, U01MH109532)
  • National Institute on Drug Abuse (K02DA032573)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Keywords
Psychiatric Genomics Consortium, psychiatric genetics, open science, therapeutic target, complex traits, precision medicine, genetic discovery
MeSH terms
Pharmacogenomic Variants, Mental Disorders, Humans, Psychiatry, Psychotropic Drugs, Genomics, Genome-Wide Association Study

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