Psychiatric disorders and neurodevelopmental conditions can be inherited through our genes and can be traced back to specific areas on our genome.
In 2007, thousands of researchers from around the world banded together, forming the Psychiatric Genomics Consortium. The goal of the group is to better understand the underlying genetic pathways of psychiatric disorders and to develop more effective therapies for schizophrenia, depression, eating disorders, and more.
A new update, co-led by Cynthia Bulik, PhD, Distinguished Professor of Eating Disorders in the Department of Psychiatry in the UNC School of Medicine and professor of nutrition at the Gillings School of Global Public Health, and anchored by Patrick Sullivan, MD, FRANZCP, the Ray M. Hayworth Distinguished Professor of Psychiatry and Genetics, introduces next steps for the consortium and describes major findings from the past half decade by the group of researchers.
"The next phase of PGC science will widen the scope of genetic discoveries for multiple psychiatric disorders and their responses to treatment," wrote Bulik, who is also founder and co-chair of the Eating Disorders Working Group of the PGC. "Our work will drive advancements across the field, establish a robust platform for future research, inspire innovation, and promote collaborative, transparent, and reproducible science to enhance clinical impact."
From Twin Studies to Genome-Wide Association Studies
Cynthia Bulik, PhD
Life experiences, environment, and genetics can all influence psychiatric disorders, but much of it comes down to variations in our genetics. Back in the 1940's, researchers used twins to study how a mental disorder is passed on by comparing the occurrence of epilepsy and schizophrenia in fraternal and identical twins.
But, with the advent of major technological innovation in genetics and large longitudinal studies, researchers now perform genome-wide association studies (GWAS) to study the genetic factors that cause psychiatric and neurodevelopmental disorders. This type of study compares DNA samples from thousands and even hundreds of thousands of people with a disorder to similarly large groups of people without that disorder.
By comparing their genomes, they can identify differences between the cases and controls to find locations on the genome that differ. Those locations are then said to be associated with the disorder or trait under study. It basically shines the light on where to dig deeper to identify implicated genes.
Schizophrenia, Major Depression Disorder, and Anorexia
In 2022, PCG researchers used a GWAS to identify 287 distinct locations on the genome that were associated with schizophrenia. Three years later, researchers filled a big gap in their understanding of major depressive disorder, which for years lagged behind other psychiatric disorders in pinpointing its associations in the genome. Using 688,808 multi-ancestry cases and over four million controls, researchers were able to connect 635 locations on the genome with the condition.
In 2019, the PGC eating disorders workgroup revolutionized our understanding of the biology of anorexia nervosa, revealing both psychiatric and metabolic genetic components and coining the term "metabo-psychiatric disorder."
Pleiotropy and Uncommon Variants
Over the past few years, scientists have found that there are common genetic threads that may be linking and causing coexisting psychiatric disorders. The impact of these uncommon and rare variants, and the extent to which they aggregate with and augment the effects of polygenicity was a core focus of the group over the past five years.
In 2019, researchers at the PGC identified 136 "hot spots" within the genome that are associated with autism spectrum disorder, attention deficit/hyperactivity disorder, schizophrenia, bipolar disorder, major depressive disorder, Tourette syndrome, obsessive-compulsive disorder, and anorexia nervosa. Of them, 109 of the hot spots were shared among multiple disorders, or were deemed "pleiotropic".
Substance Use Disorder
Similarly, noticing that problems with alcohol, tobacco, cannabis and opioids tend to co-occur with each other, members of the PGC found 19 genetic signals that were related to multiple substance use problems and other hotspots that only influenced one substance.
Researchers can now use this knowledge to search for medications that were associated with the expression changes caused by these pleiotropic signals-a starting point for future discoveries that might improve our ability to treat substance use disorders.
Autism Spectrum Disorder and Intellectual Disability
They specifically homed in on genetic errors that are caused by the duplication or deletion of DNA segments, termed copy number variants, or CNVs. In 2023, the PGC identified CNVs in NRXN1, a gene well-documented for its role in autism spectrum disorder and intellectual disability, and a deletion in ABCB11, which plays a role in one's ability to response to antipsychotic medications.
Improved Clinical Care and Data Sharing
Genome locations indicated by GWAS can comprise multiple significant and correlated variants, but the data tell little about the biology underlying these hot spots. Researchers decided to incorporate protein data into their GWAS studies to offer insights into commonalities and differences between psychiatric disorders at the molecular and cellular level.
For example, a 2025 study in Nature found that bipolar disorder was associated with higher expression of genes in neurons important in emotional processing, memory, altered inhibition or excitability of brain processing, digestion and metabolism, and hormone regulation.
But the PGC doesn't just produce data, it shares it with the wider genetic and psychiatric communities, too. Their data from 50+ GWAS studies have been accessed >154,000 times since 2021, and has made it into many genomic, functional genomic, and biological studies across the field.
Future Endeavors for the PGC
The PGC aims to widen the scope of genetic discoveries for multiple psychiatric disorders to include responses to treatment, as well as psychiatric disorders across the lifespan and across populations.
Using both genetics and other sources of environmental, clinical, and neuroscience data, the PGC's plan to take a lifespan approach to understand disorders typically onsetting in childhood (e.g., autism spectrum disorder), adulthood (e.g., substance use disorder), and later life (e.g., Alzheimer's) and examine the longitudinal course of psychiatric health and resilience in populations.
The update was co-led by Arpana Agrawal, PhD, The James and Juanita Wittmer Professor of Psychiatry, Washington University in St. Louis School of Medicine.
