MDD Working Group Leadership
About Us
Our History
The MDD workgroup has been a part of the Psychiatric Genomics Consortium from its beginning circa 2007. Since then, we have grown to include over 350 scientists from more than 30 countries around the world. Our interdisciplinary membership ranges from distinguished faculty to junior investigators from all of the academic disciplines required for this collaborative work, including epidemiology, statistical genetics, and clinical psychiatry/psychology.
Our Motivation
Depression, including major depression (MDD), affects over 300 million individuals worldwide, and represents a leading cause of disability worldwide. People who are depressed may experience profound sadness, lose interest in life activities, have difficulty sleeping or concentrating, and may even think about or attempt suicide.
It has long been observed that depression runs in families. Research on twins (who share either 50% or 100% of their genetic information) has found that 30-50% of differences in risk for depression can be explained by genetic factors. This PGC MDD workgroup seeks to identify which specific parts of our genetic code contribute to this debilitating condition and its consequences—and how.
For more information on major depression, see our list of compiled resources.
Major Accomplishments
Latest Results
The genomics o f depression are notoriously complex, requiring very large samples to detect meaningful effects across the entire genome.
Our most recent effort to advance the genetics of major depression brought together the largest and most ancestrally diverse dataset to date, using genetic data of more than five million people across 29 countries worldwide (nearly 700,000 individuals with depression), with nearly 25% of participants coming from non-European backgrounds and admixed populations. This global collaboration, led by the PGC MDD working group, identified 697 genetic variants with 293 novel loci and implicated 308 genes in depression risk—marking a significant step forward in uncovering its biological underpinnings. The study was published in 2025 in Cell.
The study improved the predictive accuracy of polygenic risk scores (from less than 2% to nearly 6% of risk variance explained). Functional analyses of associated genes highlighted key postsynaptic processes such as calcium signaling and endocytosis and implicated a range of neuronal cell types spanning excitatory, inhibitory, and regional populations (e.g., amygdala, thalamus, hippocampus). Importantly, several mapped genes overlapped with targets of existing medications, including antidepressants and drugs used for sleep and pain, pointing to new therapeutic opportunities.
Together, these findings underscore the value of large-scale, multi-ancestry genomic approaches and reinforce the importance of expanding representation in future research to ensure precision medicine benefits all populations globally.
Publications
Adams, Mark J., et al. (2025) in Cell: Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies. https://www.cell.com/cell/fulltext/S0092-8674(24)01415-6
Meng, X., Navoly, G., Giannakopoulou, O., Levey, D. F., Koller, D., Pathak, G. A., ... & Kuchenbaecker, K. (2024) in Nature Genetics: Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference. https://doi.org/10.1038/s41588-023-01568-3
Adams, M. J., Thorp, J. G., Jermy, B. S., Kwong, A. S., Kõiv, K., Grotzinger, A. D., ... & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. (2024) in Psychological Medicine: Genome-wide meta-analysis of ascertainment and symptom structures of major depression in case-enriched and community cohorts. https://doi.org/10.1017/S0033291723001094
Guintivano, J., Byrne, E. M., Kiewa, J., Yao, S., Bauer, A. E., Aberg, K. A., ... & Sullivan, P. (2023) in American Journal of Psychiatry: Meta-analyses of genome-wide association studies for postpartum depression. https://doi.org/10.1176/appi.ajp.20230045
Pain, O., Hodgson, K., Trubetskoy, V., Ripke, S., Marshe, V. S., Adams, M. J., ... & Posthuma, D. (2022) in Biological Psychiatry Global Open Science: Identifying the common genetic basis of antidepressant response. https://doi.org/10.1016/j.bpsgos.2022.01.003
Kendall, K. M., Van Assche, E., Andlauer, T. F. M., Choi, K. W., Luykx, J. J., Schulte, E. C., & Lu, Y. (2021) in Psychological Medicine: The genetic basis of major depression. https://doi.org/10.1017/S0033291721000441
McIntosh, A. M., Sullivan, P. F., & Lewis, C. M. (2019) in Neuron: Uncovering the genetic architecture of major depression. https://doi.org/10.1016/j.neuron.2019.03.022
Work with us!
If you have questions regarding the PGC MDD workgroup or projects that are currently being conducted, please contact the workgroup chairs.
For any questions or ideas related to research dissemination (e.g., via this webpage, social media, blogs, press outlets), please contact the workgroup outreach liaison.
If you have questions about how to access summary statistics or genotype-level data, or are interested in submitting a secondary analysis proposal, please contact the workgroup data access committee representative.
Get Involved!
We welcome new collaborators with studies on depression with genomic data, to continue our work in identifying the genetic contribution to depression and related phenotypes. We are committed to better representation of all ancestries.
If you would like to be a part of these efforts, please contact the respective representatives below:
MDD STUDIES
COPY NUMBER VARIANT
Postpartum Depression
ECT RESPONSE
MDD TREATMENT RESPONSE
MDD HETEROGENEITY
LIFECOURSE AND LONGITUDINAL
Funders
