Defining suicidality phenotypes for genetic studies: perspectives of the Psychiatric Genomics Consortium Suicide Working Group.
| Title: | Defining suicidality phenotypes for genetic studies: perspectives of the Psychiatric Genomics Consortium Suicide Working Group. |
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| Authors: | Colbert SMC; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. sarah.colbert@icahn.mssm.edu.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. sarah.colbert@icahn.mssm.edu.; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. sarah.colbert@icahn.mssm.edu.; Monson ET; Department of Psychiatry, University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, UT, USA.; Huntsman Mental Health Institute, Salt Lake City, UT, USA.; Andreassen OA; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.; NORMENT Centre, University of Oslo, Oslo, Norway.; Ayinde OO; Department of Psychiatry, College of Medicine, University of Ibadan, Ibadan, Nigeria.; Barr PB; Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.; VA New York Harbor Healthcare System, New York, NY, USA.; Institute for Genomics in Health, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.; Department of Epidemiology and Biostatistics, School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.; Bejan CA; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.; Ceja Z; Mental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Coon H; Department of Psychiatry, University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, UT, USA.; Huntsman Mental Health Institute, Salt Lake City, UT, USA.; DiBlasi E; Department of Psychiatry, University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, UT, USA.; Huntsman Mental Health Institute, Salt Lake City, UT, USA.; Edenberg HJ; Department of Medical & Molecular Genetics, Indiana University, Bloomington, IN, USA.; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Bloomington, IN, USA.; Gelernter J; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; Department of Psychiatry, VA CT Healthcare System, West Haven, CT, USA.; Hatoum A; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.; Izotova A; Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway.; PsychGen Centre for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.; Department of Psychology, University of Oslo, Oslo, Norway.; Johnson EC; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.; Kaufman EA; Department of Psychiatry, University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, UT, USA.; Huntsman Mental Health Institute, Salt Lake City, UT, USA.; Kranzler HR; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.; Mental Illness Research, Education and Clinical Center, Crescenz VA Medical Center, Philadelphia, PA, USA.; Koromina M; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Lehto K; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.; Myung W; Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.; Department of Psychiatry, Seoul National University College of Medicine, Seongnam, South Korea.; Nurnberger JI Jr; Department of Medical & Molecular Genetics, Indiana University, Bloomington, IN, USA.; Department of Psychiatry, Indiana University School of Medicine, Bloomington, IN, USA.; Serretti A; Department of Medicine and Surgery, Kore University of Enna, Enna, Italy.; Oasi Research Institute-IRCCS, Troina, Italy.; Smoller JW; Center for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.; Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, MA, USA.; Stein MB; Department of Psychiatry and School of Public Health, University of California San Diego, La Jolla, CA, USA.; Zai CC; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.; Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.; Erlangsen A; Center of Mental Health Research, Australian National University, Canberra, ACT, Australia.; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Danish Research Institute for Suicide Prevention, Mental Health Centre Copenhagen, Copenhagen, Denmark.; Gaine M; The Department of Pharmaceutical Sciences and Experimental Therapeutics (PSET), College of Pharmacy, University of Iowa, Iowa City, IA, USA.; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA.; Martorell L; Research department, Hospital Universitari Institut Pere Mata, IISPV-CERCA, Reus, Spain.; Psychiatry Unit, Universitat Rovira i Virgili, Reus, Spain.; Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.; Sud R; Center for Brain and Mind, Department of Psychiatry, NIMHANS, Bangalore, India.; Molecular Genetics Laboratory, Department of Psychiatry, NIMHANS, Bangalore, India.; Toma C; Centre for Molecular Biology Severo Ochoa (CBMSO), The Spanish National Research Council (CSIC) & Autonomous University of Madrid, Madrid, Spain.; Neuroscience Research Australia, Sydney, NSW, Australia.; School of Clinical Medicine, Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, NSW, Australia.; Bigdeli TB; Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.; VA New York Harbor Healthcare System, New York, NY, USA.; Institute for Genomics in Health, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.; Department of Epidemiology and Biostatistics, School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.; Kimbrel NA; Durham VA Health Care System, Durham, NC, USA.; VA Health Services Research and Development Center of Innovation to Accelerate Discovery and Practice Transformation, Durham, NC, USA.; VISN 6 Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham, NC, USA.; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.; Ruderfer D; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Genetics Institute, Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.; Docherty AR; Department of Psychiatry, University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, UT, USA.; Huntsman Mental Health Institute, Salt Lake City, UT, USA.; Clinical and Translational Science Institute & the Center for Genomic Medicine, University of Utah, Salt Lake City, UT, USA.; Mann JJ; Departments of Psychiatry and Radiology, Columbia University, New York, NY, USA.; Mullins N; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. niamh.mullins@mssm.edu.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. niamh.mullins@mssm.edu.; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. niamh.mullins@mssm.edu. |
| Corporate Authors: | Psychiatric Genomics Consortium Suicide Working Group |
| Source: | Molecular psychiatry [Mol Psychiatry] 2025 Dec; Vol. 30 (12), pp. 6144-6154. Date of Electronic Publication: 2025 Sep 25. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5578 (Electronic) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals; Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996- |
| MeSH Terms: | Suicide*/psychology; Genome-Wide Association Study/methods ; Suicide, Attempted/psychology ; Genomics/methods ; Mental Disorders/genetics ; Genetic Predisposition to Disease/genetics ; Humans ; Phenotype ; Suicidal Ideation |
| Abstract: | Suicidality phenotypes, consisting of suicidal ideation (SI), suicide attempt (SA), and suicide death (SD), are all heritable but present unique challenges in genome-wide association studies (GWAS) due to their individual complexity, overlap with each other and with related self-harm phenotypes, and varying associations with psychiatric disorders. GWAS have uncovered several loci associated with suicidality phenotypes by meta-analyzing data from multiple cohorts. However, combining datasets from many research groups, where each group may use different study designs, phenotyping instruments, and definitions of suicidality phenotypes, presents challenges. Heterogeneity resulting from these differences can limit genetic discovery; harmonizing phenotype definitions to ensure consistency will greatly improve results. Here, we describe a standardized phenotyping protocol that draws on the expertise of a subgroup of clinicians, researchers, and experts from the Psychiatric Genomics Consortium Suicide Working Group to propose consensus definitions for SI, SA, and SD for genetic studies.; (© 2025. The Author(s).) |
| Competing Interests: | Competing interests: Ole Andreassen: Consultant to Cortechs.ai and Precision-Health.ai, and received speaker’s honorarium from Lundbeck, Sunovion, Janssen and Otsuka. Murray Stein: MBS has in the past 3 years received consulting income from Aptinyx, atai Life Sciences, BigHealth, Biogen, Bionomics, Boehringer Ingelheim, Delix Therapeutics, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, Karuna Therapeutics, Lykos Therapeutics, NeuroTrauma Sciences, Otsuka US, PureTech Health, Sage Therapeutics, Seaport Therapeutics, and Roche/Genentech. Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He has been paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). He is on the scientific advisory board of the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America. John Mann: Dr. Mann receives royalties for commercial use of the C-SSRS from the Research Foundation of Mental Hygiene and from Columbia University for the Columbia Pathways App. Jordan Smoller: Dr. Smoller is a member of the Scientific Advisory Board of Sensorium Therapeutics (with options), and has received grant support from Biogen, Inc. He is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments. Henry Kranzler: Dr. Kranzler is a member of advisory boards for Altimmune and Clearmind Medicine; a consultant to Sobrera Pharmaceuticals; the recipient of research funding and medication supplies for an investigator-initiated study from Alkermes; a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which was supported in the last three years by Alkermes, Dicerna, Ethypharm, Imbrium, Indivior, Kinnov, Lilly, Otsuka, and Pear; and an inventor on U.S. provisional patent “Multi-ancestry Genome-wide Association Meta-analysis of Buprenorphine Treatment Response”. All other listed authors declare no conflicts of interest. |
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| Grant Information: | P30 ES005605 United States ES NIEHS NIH HHS; 1842169 National Science Foundation (NSF); R01 MH132733 United States MH NIMH NIH HHS; R01MH132733 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH); K23 MH135225 United States MH NIMH NIH HHS |
| Contributed Indexing: | Investigator: SM Colbert; O Ayinde; AS Hatoum; DM Ruderfer; M Adams; R Adolfsson; I Agartz; E Agerbo; TM Air; M Alda; L Alfredsson; A Anjorin; V Appadurai; MS Artigas; AE Ashley-Koch; S Awasthi; MH Azevedo; EB García; A Bakian; N Bass; CH Bau; BT Baune; JC Beckham; F Bellivier; AW Bergen; K Berger; WH Berrettini; JM Biernacka; TB Bigdeli; EB Binder; M Boehnke; M Bohus; MP Boks; AD Børglum; R Bosch; DL Braff; H Brandt; G Breen; R Bryant; M Budde; CM Bulik; EM Byrne; W Cahn; AI Campos; M Casas; E Castelao; JA Cervilla; X Chang; B Chaumette; HC Chen; WJ Chen; ED Christensen; S Cichon; JRI Coleman; A Corvin; N Craddock; D Craig; S Crawford; S Crow; F Degenhardt; D Demontis; M Dennis; S Djurovic; P Duriez; A Edwards; T Esko; G Fanelli; AH Fanous; F Fernández-Aranda; MM Fichter; JC Foo; AJ Forstner; GR Fries; M Frye; JM Fullerton; H Galfalvy; S Gallinger; M Gandal; M Garrett; JM Gatt; PV Gejman; I Giegling; SJ Glatt; P Gorwood; HJ Grabe; MJ Green; EH Grevet; M Grigoroiu-Serbanescu; Y Guo; B Gutierrez; A Gutierrez-Zotes; J Guzman-Parra; JD Hafferty; L Hair; H Hakonarson; KA Halmi; SP Hamilton; ML Hamshere; AM Hartmann; P Harvey; ER Hauser; MA Hauser; J Hauser; S Heilmann-Heimbach; A Hishimoto; P Hoffmann; DM Hougaard; J Huffman; HG Hwu; M Ising; D Jacobson; S Jain; S Jamain; M Ji; S Jiménez-Murcia; C Johnson; I Jones; LA Jones; L Jonsson; RS Kahn; J Kang; AS Kaplan; WH Kaye; PK Keel; JR Kelsoe; KS Kendler; JL Kennedy; RC Kessler; M Kim; S Kloiber; KL Klump; KC Koenen; M Kogevinas; B Konte; MO Krebs; PH Kuo; M Landén; S Lannoy; J Lawrence; M Leboyer; PH Lee; DF Levey; DF Levinson; CM Lewis; D Li; QS Li; SC Liao; C Liao; K Lieb; L Lilenfeld; JH Lindquist; J Lissowska; CM Liu; A Lori; S Lucae; R Madduri; PJ Magistretti; CR Marshall; NG Martin; F Mayoral; SL McElroy; P McGrath; P McGuffin; AM McIntosh; B McMahon; A McQuillin; SE Medland; D Mehta; I Melle; Y Milaneschi; JE Mitchell; PB Mitchell; E Molina; G Morken; O Mors; PB Mortensen; B Müller-Myhsok; G Muntané; B Murnyak; RM Myers; C Nievergelt; V Nimgaonkar; M Nordentoft; MM Nöthen; MC O'Donovan; S Okazaki; CM Olsen; RA Ophoff; DW Oslin; I Otsuka; MJ Owen; S Papiol; C Pato; MT Pato; BW Penninx; J Pimm; D Pinto; G Pistis; R Polimanti; D Porteous; JB Potash; RA Power; A Powers; M Preisig; X Qin; D Quested; JA Ramos-Quiroga; N Ramoz; A Reif; ME Rentería; M Ribasés; V Richarte; M Rietschel; S Ripke; M Rivera; A Roberts; G Roberts; S Roepke; GA Rouleau; DL Rovaris; V Rozanov; D Rujescu; V Sànchez-Gistau; C Sánchez-Mora; AR Sanders; C Sawyers; SW Scherer; C Schmahl; PR Schofield; TG Schulze; LJ Scott; A Shabalin; J Shi; SI Shyn; L Sirignano; P Sklar; OB Smeland; DJ Smith; M Sokolowski; EJS Sonuga-Barke; G Spalletta; EA Stahl; A Starnawska; M Stephenson; JS Strauss; F Streit; M Strober; MH Su; B Świątkowska; LM Thornton; J Trafton; J Treasure; M Trzaskowski; MT Tsuang; G Turecki; RJ Ursano; S Van der Auwera; L Vilar-Ribó; E Vilella; JB Vincent; H Völzke; C Walss-Bass; JT Walters; EB Ware; D Wasserman; HJ Watson; CS Weickert; TW Weickert; MM Weissman; F Wendt; T Werge; DC Whiteman; LM Williams; V Willour; SH Witt; DB Woodside; NR Wray; Z Yilmaz; L Zillich |
| Entry Date(s): | Date Created: 20250925 Date Completed: 20251112 Latest Revision: 20260307 |
| Update Code: | 20260307 |
| PubMed Central ID: | PMC12602352 |
| DOI: | 10.1038/s41380-025-03271-y |
| PMID: | 40999039 |
| Database: | MEDLINE |
Journal Article; Review