Year: 2025
Type: review
Abstract: Research by the Psychiatric Genomics Consortium (PGC) has advanced the discovery of common and rare genetic variations that contribute to the susceptibility to many psychiatric disorders and neurodevelopmental conditions. This Review reflects on major findings from the past 5 years of research by the PGC in five priority areas: discovery of common variants using genome-wide association studies; rare variation and its interplay with polygenic risk; using genetics to go beyond diagnostic boundaries; ascribing functional attributes to genomic discoveries; and developing and implementing processes for data sharing, outreach to various communities, and training. The insights gained in these domains frame the agenda for the next phase of PGC research. In addition to accelerating integrative findings of common and rare variants within, and across, multiple psychiatric disorders and neurodevelopmental conditions, the next phase will use multiple populations to elucidate genetic causes, integrate results with rapidly accumulating multimodal functional genomics data to gain mechanistic understanding, convert genetic findings to clinically actionable phenotypes, such as treatment response, and address the emerging use of polygenic scores. Together, these next steps will highlight the biological underpinnings of psychiatric disorders and neurodevelopmental conditions, which continue to contribute to global morbidity and mortality.
Source: The Lancet Psychiatry
Authors: Arpana Agrawal, Cynthia M Bulik, Dawit Shawel Abebe, Ole A Andreassen, Elizabeth G Atkinson, Karmel W Choi, Aiden Corvin, Helena L Davies, Lea K Davis, Anna R Docherty, Howard J Edenberg, Barbara Franke, Joel Gelernter, Paola Giusti-Rodríguez, John M Hettema, Jens Hjerling-Leffler, Hailiang Huang, Emma C Johnson, Cathryn M Lewis, Yi Lu, Mary-Ellen Lynall, Joanna Martin, Andrew M McIntosh, Janitza L Montalvo-Ortiz, Niamh Mullins, Caroline M Nievergelt, Kevin S O'Connell, Michael C O'Donovan, Adeniran Okewole, Roseann E Peterson, Danielle Posthuma, Jonathan Sebat, Jordan W Smoller, Reeteka Sud, Biju Viswanath, James T R Walters, Hyejung Won, Naomi R Wray, Patrick F Sullivan
Institutions: Washington University in St. Louis, University of North Carolina at Chapel Hill, Karolinska Institutet, OsloMet – Oslo Metropolitan University, Innlandet Hospital Trust, Oslo University Hospital, University of Oslo, Baylor College of Medicine, Texas Children's Hospital, Harvard University, Massachusetts General Hospital, Trinity College Dublin, Sankt Hans Hospital, Mental Health Services, Copenhagen University Hospital, Icahn School of Medicine at Mount Sinai, University of Utah, Indiana University Indianapolis, Indiana University School of Medicine, Indiana University – Purdue University Indianapolis, Radboud University Nijmegen, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Yale University, VA Connecticut Healthcare System, University of Florida Health, University of Florida, Texas A&M University, Broad Institute, Stanley Center for Psychiatric Research, King's College London, University of Cambridge, Cardiff University, University of Edinburgh, University of California San Diego, VA San Diego Healthcare System, Center of Excellence for Stress and Mental Health, SUNY Downstate Health Sciences University, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Massachusetts Institute of Technology, National Institute of Mental Health and Neurosciences, The University of Queensland, University of Oxford, Institute for Molecular Bioscience
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: U.S. Department of Veterans Affairs, Brain and Behavior Research Foundation, Stiftelsen Kristian Gerhard Jebsen, Wellcome Trust, European Commission, Department of Biotechnology, Ministry of Science and Technology, India, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Hjärnfonden, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, NordForsk, Norges Forskningsråd, The Wellcome Trust DBT India Alliance, Novo Nordisk Fonden, National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: All of Us Coast-to-Coast Strong recrUitment, Retention, and Facilitation (C2C SURF), Genome-Wide Association Analysis of Suicide Death, Eating Disorders Genetics Initiative (EDGI), G2884242354, G4882694058, Genetic Architecture of Avoidant/Restrictive Food Intake Disorder, Deciphering the molecular mechanisms of lithium response in patients with bipolar disorder, Understanding the transgenerational epigenetic effect of maternal psychosocial trauma exposure on infants via lncRNA-sequencing, Growing Up Together in Society (GUTS), 4/9: Dissecting the effects of genomic variants on neurobehavioral dimensions in CNVs enriched for neuropsychiatric disorders, Empowering gene discovery and accelerating clinical translation for admixed populations, 7/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact, Establishing the Suicide Working Group of the Psychiatric Genomics Consortium to elucidate the genetics and biology of suicide outcomes, Deciphering the single-nucleus genomic regulatory structure of opioid use disorder in the human brain, 3/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact, 1/3 Eating Disorders Genetics Initiative 2 (EDGI2), 5/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact, 4/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact, Psychiatric Genomics Consortium for PTSD, Integrating developmental and genomic approaches to identify early trajectories of eating and internalizing disorder symptoms, 1/7 PGC: Advancing Discovery and Impact, 2/2 TRANS-ANCESTRY GENOMIC ANALYSIS OF OBSESSIVE COMPULSIVE DISORDER, Cross-Population Working Group on Genes and Environment in Major Depression (POP-GEM): Advancing the Understating of Etiology through Diversity, 6/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact, Identifying genetic sources of comorbidity between cannabis and schizophrenia using genome-wide and integrative omics data, 2/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact, Genetics of PTSD in African Ancestry Populations, Beyond GWAS: High Throughput Functional Genomics & Epigenome Editing to Elucidate the Effects of Genetic Associations for Schizophrenia, Genetic Basis of the Risk and Consequences of Cannabis Exposure in Humans, Discovery and validation of genetic variation impacting the gene regulatory landscape during human cortical development
OpenAlex ID: W4411678591