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Review
. 2025 Dec;30(12):6144-6154.
doi: 10.1038/s41380-025-03271-y. Epub 2025 Sep 25.

Defining suicidality phenotypes for genetic studies: perspectives of the Psychiatric Genomics Consortium Suicide Working Group

Sarah M C Colbert  1   2   3 , Eric T Monson  4   5 , Ole A Andreassen  6   7 , Olatunde O Ayinde  8 , Peter B Barr  9   10   11   12 , Cosmin A Bejan  13 , Zuriel Ceja  14   15 , Hilary Coon  4   5 , Emily DiBlasi  4   5 , Howard J Edenberg  16   17 , Joel Gelernter  18   19 , Alexander Hatoum  20 , Anastasia Izotova  21   22   23 , Emma C Johnson  20 , Erin A Kaufman  4   5 , Henry R Kranzler  24   25 , Maria Koromina  26   27   28 , Kelli Lehto  29 , Woojae Myung  30   31 , John I Nurnberger Jr  16   32 , Alessandro Serretti  33   34 , Jordan W Smoller  35   36   37 , Murray B Stein  38 , Clement C Zai  36   39   40   41   42 , Annette Erlangsen  43   44   45 , Marie Gaine  46   47 , Lourdes Martorell  48   49   50 , Reeteka Sud  51   52 , Claudio Toma  53   54   55 , Tim B Bigdeli  9   10   11   12 , Nathan A Kimbrel  56   57   58   59 , Douglas Ruderfer  13   60   61 , Anna R Docherty  4   5   62 , J John Mann  63 , Niamh Mullins  64   65   66 ; Psychiatric Genomics Consortium Suicide Working Group
Collaborators, Affiliations
Review

Defining suicidality phenotypes for genetic studies: perspectives of the Psychiatric Genomics Consortium Suicide Working Group

Sarah M C Colbert et al. Mol Psychiatry. 2025 Dec.

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.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1. Schematic of comparison between SA cases versus potential control groups with varying prevalence of psychiatric disorders.
A–C The left panels represent SA cases, and the right panels represent the control group. Amongst SA cases, the prevalence of psychiatric disorders is 0.9. A The population control group displays psychiatric disorders at a prevalence of 0.3 and SA at a prevalence of 0.02. B The SA-screened control group displays psychiatric disorders at a prevalence of 0.3. C The non-psychiatric control group assumes a prevalence of 0 for both psychiatric disorders and SA.
See this image and copyright information in PMC

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