Cross Disorder Analyses Working Group Leadership
Work with us!
Our group calls are open to the full PGC membership. We are especially interested in future members who bring methodological expertise that could help characterize the shared and unique genetic signal across disorders.
Members of the working group stay connected through regular conference calls (first Wednesday of the month, oscillating between 9-10 am and 3-4 pm East Coast U.S. time). If you are interested in joining our group calls, have questions about our group, or are interested in starting a cross-disorder project, please contact Andrew Grotzinger and Wouter Peyrot.
About Us
Our History
The Cross-Disorder working group of the PGC was founded in 2008 by Drs. Jordan Smoller and Ken Kendler. Drs. Wouter Peyrot and Andrew Grotzinger stepped in as co-chairs in 2026. The working group includes representatives from each of the individual PGC disorder groups, along with members who bring expertise in statistical and psychiatric genetics, clinical practice, methods development, and functional annotation.
Our Motivation
The Cross-Disorder working group of the PGC was founded in 2008 by Drs. Jordan Smoller and Ken Kendler. Drs. Wouter Peyrot and Andrew Grotzinger stepped in as co-chairs in 2026. The working group includes representatives from each of the individual PGC disorder groups, along with members who bring expertise in statistical and psychiatric genetics, clinical practice, methods development, and functional annotation.
Most individuals that are diagnosed with a psychiatric disorder will receive multiple diagnoses in their lifetime. This co-occurrence is also reflected in genetic risk, with high genetic correlations observed across a range of childhood- and adult-onset psychiatric disorders. Analyses led by the Cross-Disorder group have identified and characterized pleiotropic genetic variants associated with multiple disorders (PMID 23933821, 31835028) and review papers have considered challenges and solutions for cross-disorder genetic research (PMID 39730880).
Our most recent effort, published in Nature in 2026 (PMID 41372416), described the convergent and divergent risk pathways across 14 psychiatric disorders. We identified five “genomic factors” that explained the majority of the genetic signal in the disorders and connected different subsets of conditions. These five factors reflected: (i) disorders with compulsive features such as anorexia nervosa, Tourette disorder and OCD, (ii) schizophrenia and bipolar disorder, (iii) neurodevelopmental conditions, including autism and ADHD, (iv) internalizing conditions including depression, anxiety and PTSD, and (v) substance use conditions. The factors were associated with 238 genetic variants and these variants implicated key pathways in the brain. For the schizophrenia and bipolar disorder factor, these pathways include genes expressed in excitatory neurons, while genes expressed in brain cells called oligodendrocytes were more prominent for the internalizing factor. Summary statistics for the five factors are publicly available for download on the PGC website.
Flagship CDG Publications
Cross-Disorder Group of the Psychiatric Genomics Consortium, Grotzinger, A.D., Werme, J., Peyrot, W.J., Frei, O., de Leeuw, C., Bicks, L.K., … Kendler, K.S., & Smoller, J.W. (2026) in Nature. Mapping the genetic landscape across 14 psychiatric disorders. https://doi.org/10.1038/s41586-025-09820-3
Cai, N., Verhulst, B., Andreassen, O.A., Buitelaar, J., Edenberg, H.J., Hettema, J.M., ... Smoller, J.W. & Kendler, K.S. (2025) in Molecular Psychiatry. Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research.https://doi.org/10.1038/s41380-024-02878-x
Cross-Disorder Group of the Psychiatric Genomics Consortium, Lee, P H., Anttila, V., Won, H., Feng, Y.C.A., Rosenthal, J., Zhu, Z., ... Kendler, K.S., & Smoller, J.W. (2019) in Cell. Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders.http://doi.org/10.1016/j.cell.2019.11.020
Cross-Disorder Group of the Psychiatric Genomics Consortium, Lee, S.H., Ripke, S., Neale, B. M., Faraone, S.V., Purcell, S.M., … Smoller, J.W., Kendler, K.S., & Wray, N.R. (2013) in Nature Genetics. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. http://doi.org/10.1038/ng.2711
Solovieff, N., Cotsapas, C., Lee, P.H., Purcell, S.M., & Smoller, J.W. (2013) in Nature Reviews Genetics. Pleiotropy in complex traits: challenges and strategies. http://doi.org/10.1038/nrg3461
Funders
