The Psychiatric Genomics Consortium (http://pgc.unc.edu), now in its eighth year, is one of the most innovative experiments in the history of psychiatry. We have unified much of the field to enable rapid progress in elucidating the genetic basis of psychiatric disorders. We have 800+ investigators from 36 countries and >400K subjects. The PGC has attracted a cadre of outstanding scientists whose careers center on our work. The PGC has published 17 main papers plus 31 secondary analysis/methods development papers. The most important was the landmark Nature paper identifying 108 loci for schizophrenia (SCZ). Due to our open-source approach, there are 75+ papers that use PGC results, and we know of numerous groups that are using our findings to direct basic and applied research (including therapeutic development). More work is needed. Large amounts of new data will be available to the PGC in the next five years (largely without NIMH funding). We have developed a rigorous set of approaches that are yielding discoveries for all of the initial five disorders (which led to adding four new disorders). We thus have the unique opportunity to rapidly and efficiently increase our knowledge of common and rare variation in order to understand the causes and comorbidities of major psychiatric disorders. Our overarching goal is to identify actionable variation via the empirical evaluation of the etiological, clinical, nosological, therapeutic, and biological significance of our genomic findings. We will continue the highly successful work of the PGC in understanding the roles of common genetic variation by: (a) comprehensively analyzing historically large GWA samples for nine major psychiatric disorders; (b) evaluating how genetic risk scores impact development and clinical symptom patterns; (c) understand the genetic relationship among psychiatric disorders and across psychiatric disorders and many other CNS diseases. We will enhance our work on the discovery of rare variation by: (d) conducting mega-analyses of copy number variation across nine psychiatric disorders; (e) efficiently and inexpensively re-sequencing regions implicated by GWAS (200 candidate genes in 20,000 subjects); and (f) using the hundreds of clinicians in the PGC, identify rare densely affected pedigrees to enable searches for rare variants of strong effect. Successful completion of this body of work will advance knowledge of the genetic basis of multiple psychiatric disorders. Our goal is to deliver actionable findings, genomic results tht (a) reveal the fundamental biology, (b) inform clinical practice, and (c) deliver new therapeutic targets. This is the central idea of the PGC: to convert the family history risk factor into biologically, clinically, and therapeutically meaningful insights. We have leveraged external funding from multiple sources to minimize NIMH budgetary requests.

Public Health Relevance

The Psychiatric Genomics Consortium (PGC), now in its eighth year, is one of the most innovative experiments in the history of psychiatry. We have unified much of psychiatric genomics to enable rapid progress in discovering the genetic basis of psychiatric disorders. We propose new aims to identify 'actionable' variation, findings with clear etiological, clinical, nosological, therapeutic, and biological significance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01MH109536-01
Application #
9083185
Study Section
Special Emphasis Panel (ZRG1-GGG-S (60)C)
Program Officer
Senthil, Geetha
Project Start
2016-07-01
Project End
2021-03-31
Budget Start
2016-07-01
Budget End
2017-03-31
Support Year
1
Fiscal Year
2016
Total Cost
$595,308
Indirect Cost
$235,643
Name
Icahn School of Medicine at Mount Sinai
Department
Psychiatry
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Zhang-James, Yanli; Fernàndez-Castillo, Noèlia; Hess, Jonathan L et al. (2018) An integrated analysis of genes and functional pathways for aggression in human and rodent models. Mol Psychiatry :
Sullivan, Patrick F; Agrawal, Arpana; Bulik, Cynthia M et al. (2018) Psychiatric Genomics: An Update and an Agenda. Am J Psychiatry 175:15-27
Vaudreuil, Carrie A H; Faraone, Stephen V; Di Salvo, Maura et al. (2018) The morbidity of subthreshold pediatric bipolar disorder: A systematic literature review and meta-analysis. Bipolar Disord :
Charney, A W; Ruderfer, D M; Stahl, E A et al. (2017) Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder. Transl Psychiatry 7:e993
Witt, S H; Streit, F; Jungkunz, M et al. (2017) Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia. Transl Psychiatry 7:e1155
Ratanatharathorn, Andrew; Boks, Marco P; Maihofer, Adam X et al. (2017) Epigenome-wide association of PTSD from heterogeneous cohorts with a common multi-site analysis pipeline. Am J Med Genet B Neuropsychiatr Genet 174:619-630
Marshall, Christian R (see original citation for additional authors) (2017) Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects. Nat Genet 49:27-35
Polimanti, Renato; Amstadter, Ananda B; Stein, Murray B et al. (2017) A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder. Genome Med 9:99
Breen, Gerome; Li, Qingqin; Roth, Bryan L et al. (2016) Translating genome-wide association findings into new therapeutics for psychiatry. Nat Neurosci 19:1392-1396