7/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact

Project Summary
Now in its 13th year, the Psychiatric Genomics Consortium is perhaps the most innovative and productive
experiment in the history of psychiatry. The PGC unified the field and attracted a cadre of outstanding
scientists (802 investigators from 157 institutions in 41 countries). PGC work has led to identification of ~500
genetic loci in the 11 psychiatric disorders we study. Our work has led to 320 papers, many in high-profile
journals (Nature 3, Cell 5, Science 2, Nat Genet 27, Nat Neurosci 9, Mol Psych 37, Biol Psych 25). As
summary statistics are freely available, psychiatric disorders often feature prominently in papers by non-PGC
investigators. To advance discovery and impact, we propose to continue the work of the PGC across 11
disorder groups. Considerable new data are coming in the next five years. We thus can rapidly and efficiently
increase our knowledge of the fundamental basis of major psychiatric disorders.
Aim 1: we will continue to advance genetic discovery for severe psychiatric disorders in all working groups,
systematically interface with large biobank studies to ensure maximal comparability, and aggressively promote
new studies of individuals with psychiatric disorders from diverse ancestries to increase discovery and improve
fine-mapping. Aim 2: most studies analyze common variation (Aim 1), rare CNV (Aim 2), and rare
exome/genome resequencing results (via collaboration) in isolation: we will apply an integrative framework to
rigorously evaluate the contributions of all measured types of genetic variation on risk for psychiatric disorders.
Aim 3: we will move beyond classical case-control definitions to a more biologically-based and nuanced
understanding by enabling large trans-diagnostic studies, convene trans-disciplinary teams to use genetics to
address unresolved questions about the nature of psychiatric disorders, and to promote large studies of the
severest cases seen in psychiatric practice (leveraging the global reach of PGC investigators). Aim 4: we will
work to maximize the impact of our work via translational efforts: close collaborations with neuroscience
consortia to understand the biological implications of our findings; work to identify modifiable causal risk
factors; and work to robustly predict clinical outcomes and identify patient subsets. Aim 5: we will increase
impact of our work by extending and formalizing outreach to different communities (including pharma and
biotech), via digital media (Twitter, Facebook, Wikipedia), and by developing, distributing, and updating
resources/educational material for patients, families, and medical professionals. We will convene a Scientific
Advisory Board to ensure we respond positively to those invested in our results
Successful completion of this body of work will greatly advance knowledge of the genetic basis of psychiatric
disorders with potentially major nosological and treatment implications. These goals are consistent with a core
mission of the NIMH, and the central idea of the PGC: to convert the family history risk factor into biologically,
clinically, and therapeutically meaningful insights.

Grant Number: 5R01DA054869-05
NIH Institute/Center: NIH
Principal Investigator: ARPANA AGRAWAL