Significant shared heritability underlies suicide attempt and clinically predicted probability of attempting suicide
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Abstract
Abstract Suicide accounts for nearly 800,000 deaths per year worldwide with rates of both deaths and attempts rising. Family studies have estimated substantial heritability of suicidal behavior; however, collecting the sample sizes necessary for successful genetic studies has remained a challenge. We utilized two different approaches in independent datasets to characterize the contribution of common genetic variation to suicide attempt. The first is a patient reported suicide attempt phenotype from genotyped samples in the UK Biobank (337,199 participants, 2,433 cases). The second leveraged electronic health record (EHR) data from the Vanderbilt University Medical Center (VUMC, 2.8 million patients, 3,250 cases) and machine learning to derive probabilities of attempting suicide in 24,546 genotyped patients. We identified significant and comparable heritability estimates of suicide attempt from both the patient reported phenotype in the UK Biobank (h 2 SNP = 0.035, p = 7.12×10 −4 ) and the clinically predicted phenotype from VUMC (h 2 SNP = 0.046, p = 1.51×10 −2 ). A significant genetic overlap was demonstrated between the two measures of suicide attempt in these independent samples through polygenic risk score analysis (t = 4.02, p = 5.75×10 −5 ) and genetic correlation (rg = 1.073, SE = 0.36, p = 0.003). Finally, we show significant but incomplete genetic correlation of suicide attempt with insomnia (rg = 0.34 - 0.81) as well as several psychiatric disorders (rg = 0.26 - 0.79). This work demonstrates the contribution of common genetic variation to suicide attempt. It points to a genetic underpinning to clinically predicted risk of attempting suicide that is similar to the genetic profile from a patient reported outcome. Lastly, it presents an approach for using EHR data and clinical prediction to generate quantitative measures from binary phenotypes that improved power for our genetic study.
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Polygenic risk scores for depressive symptoms, neuroticism, major depressive disorder, and schizophrenia predicted suicide attempts in about 160,000 participants.
“Ruderfer et al. found that PRS for depressive symptoms, neuroticism, major depressive disorder, and schizophrenia predicted suicide attempts in about 160,000 participants (41).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [41]
The Introduction (page unavailable) says more than 157,000 UK Biobank participants took the mental-health assessment, and the Results section on genetic correlation (page unavailable) reports positive genetic correlations between suicide attempt and all four named traits. But the paper does not report that polygenic risk scores for those four traits predicted attempts in about 160,000 participants. Its polygenic-risk-score analysis used a score derived from the UK Biobank suicide-attempt GWAS and tested it in 24,546 BioVU patients. (LLM, conf=0.88)
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Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
Regression Modeling Strategies
Harrell, F. E. (2001) · Springer series in statistics · doi:10.1007/978-1-4757-3462-1 · Cited by 9,270 · see citing works
The UK Biobank resource with deep phenotyping and genomic data
Bycroft, C., Freeman, C., Petkova, D., Band, G., Elliott, L. T., Sharp, K., Motyer, A., Vukcevic, D., Delaneau, O., O’Connell, J., et al. (2018) · Nature · doi:10.1038/s41586-018-0579-z · Cited by 8,876 · see citing works
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577 · see citing works
Harrell (2015) · Springer Series in Statistics · doi:10.1007/978-3-319-19425-7 · Cited by 6,878 · see citing works
LD Score regression distinguishes confounding from polygenicity in genome-wide association studies
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bulik-Sullivan, B. K., Loh, P.-R., Finucane, H. K., Ripke, S., Yang, J., Patterson, N., Daly, M. J., Price, A. L., & Neale, B. M. (2015) · Nature Genetics · doi:10.1038/ng.3211 · Cited by 5,559 · see citing works
(2013) · The Lancet · doi:10.1016/s0140-6736(12)62129-1 · Cited by 3,010 · see citing works
Nock, M. K., Borges, G., Bromet, E. J., Cha, C. B., Kessler, R. C., & Lee, S. (2008) · Epidemiologic Reviews · doi:10.1093/epirev/mxn002 · Cited by 2,897 · see citing works
Genome-wide association study identifies 74 loci associated with educational attainment
Okbay, A., Beauchamp, J. P., Fontana, M. A., Lee, J. J., Pers, T. H., Rietveld, C. A., Turley, P., Chen, G.-B., Emilsson, V., Meddens, S. F. W., et al. (2016) · Nature · doi:10.1038/nature17671 · Cited by 1,297 · see citing works
A mega-analysis of genome-wide association studies for major depressive disorder
Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Ripke, S., Wray, N. R., Lewis, C. M., Hamilton, S. P., Weissman, M. M., Breen, G., Byrne, E. M., Blackwood, D. H. R., Boomsma, D. I., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.21 · Cited by 1,120 · see citing works
Study, L. C., Okbay, A., Baselmans, B. M. L., De Neve, J.-E., Turley, P., Nivard, M. G., Fontana, M. A., Meddens, S. F. W., Linnér, R. K., Rietveld, C. A., et al. (2016) · Nature Genetics · doi:10.1038/ng.3552 · Cited by 1,013 · see citing works
Development of a Large-Scale De-Identified DNA Biobank to Enable Personalized Medicine
Roden, D. M., Pulley, J. M., Basford, M., Bernard, G. R., Clayton, E. W., Balser, J., & Masys, D. R. (2008) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2008.89 · Cited by 959 · see citing works
Zheng, J., Erzurumluoglu, A. M., Elsworth, B. L., Kemp, J. P., Howe, L., Haycock, P. C., Hemani, G., Tansey, K., Laurin, C., Early Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium, et al. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btw613 · Cited by 869 · see citing works
Psychiatric Risk Factors for Adolescent Suicide: A Case-Control Study
Brent, D. A., Perper, J. A., MORITZ, G., ALLMAN, C., FRIEND, A., ROTH, C., SCHWEERS, J., BALACH, L., & BAUGHER, M. (1993) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199305000-00006 · Cited by 863 · see citing works
Mental disorders and comorbidity in suicide
(1993) · American Journal of Psychiatry · doi:10.1176/ajp.150.6.935 · Cited by 861 · see citing works
Meta-analysis of sleep disturbance and suicidal thoughts and behaviors
Pigeon, W. R., Pinquart, M., & Conner, K. (2012) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.11r07586 · Cited by 815 · see citing works
Family genetic studies, suicide, and suicidal behavior
Brent, D. A., & Mann, J. J. (2005) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30042 · Cited by 618 · see citing works
Genome-wide genetic data on ~500,000 UK Biobank participantsPreprint
Bycroft, C., Freeman, C., Petkova, D., Band, G., Elliott, L. T., Sharp, K., Motyer, A., Vukcevic, D., Delaneau, O., O’Connell, J., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/166298 · Cited by 606 · see citing works
Predicting Risk of Suicide Attempts Over Time Through Machine Learning
Walsh, C. G., Ribeiro, J. D., & Franklin, J. C. (2017) · Clinical Psychological Science · doi:10.1177/2167702617691560 · Cited by 571 · see citing works
Self-citationSuicidal Behavior Runs in Families: A Controlled Family Study of Adolescent Suicide Victims
Brent, D. A. (1996) · Archives of General Psychiatry · doi:10.1001/archpsyc.1996.01830120085015 · Cited by 516 · see citing works
Suicidal behaviour: an epidemiological and genetic study
STATHAM, D. J., HEATH, A. C., MADDEN, P. A. F., BUCHOLZ, K. K., BIERUT, L., DINWIDDIE, S. H., SLUTSKE, W. S., DUNNE, M. P., & MARTIN, N. G. (1998) · Psychological Medicine · doi:10.1017/s0033291798006916 · Cited by 471 · see citing works
Kessler, R. C., Warner, C. H., Ivany, C., Petukhova, M. V., Rose, S., Bromet, E. J., Brown, M., Cai, T., Colpe, L. J., Cox, K. L., et al. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1754 · Cited by 447 · see citing works
Correcting for Optimistic Prediction in Small Data Sets
Smith, G. C. S., Seaman, S. R., Wood, A., Royston, P. J., & White, I. R. (2014) · American Journal of Epidemiology · doi:10.1093/aje/kwu140 · Cited by 354 · see citing works
Genetics of suicide: a systematic review of twin studies
Voracek, M., & Loibl, L. M. (2007) · Wiener klinische Wochenschrift · doi:10.1007/s00508-007-0823-2 · Cited by 342 · see citing works
Predicting suicidal behavior from longitudinal electronic health records.
Barak-Corren, Y., Castro, V. M., Javitt, S., Hoffnagle, A. G., Dai, Y., Perlis, R. H., Nock, M. K., Smoller, J. W., & Reis, B. Y. (2017) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.16010077 · Cited by 339 · see citing works
Lane, J. M., Liang, J., Vlasac, I., Anderson, S. G., Bechtold, D. A., Bowden, J., Emsley, R., Gill, S., Little, M. A., Luik, A. I., et al. (2016) · Nature Genetics · doi:10.1038/ng.3749 · Cited by 337 · see citing works
Genome-wide analysis identifies 12 loci influencing human reproductive behavior
Barban, N., Study, L. C., Jansen, R., de Vlaming, R., Vaez, A., Mandemakers, J. J., Tropf, F. C., Shen, X., Wilson, J. F., Chasman, D. I., et al. (2016) · Nature Genetics · doi:10.1038/ng.3698 · Cited by 315 · see citing works
Ribeiro, J. D., Pease, J. L., Gutierrez, P. M., Silva, C., Bernert, R. A., Rudd, M. D., & Joiner, T. E. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.09.049 · Cited by 304 · see citing works
Self-citationHammerschlag, A. R., Stringer, S., de Leeuw, C. A., Sniekers, S., Taskesen, E., Watanabe, K., Blanken, T. F., Dekker, K., te Lindert, B. H. W., Wassing, R., et al. (2017) · Nature Genetics · doi:10.1038/ng.3888 · Cited by 289 · see citing works
Suicidal thoughts and behaviors among adults aged ≥18 years--United States, 2008-2009.
Crosby, A. E., Han, B., Ortega, L., Parks, S. E., & GFROERER, J. (2011) · PubMed · Cited by 278 · see citing works
National trends in suicide attempts among adults in the United States.
Olfson, M., Blanco, C., Wall, M., Liu, S.-M., Saha, T. D., Pickering, R. P., & Grant, B. F. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.2582 · Cited by 229 · see citing works
Kessler, R. C., Stein, M. B., Petukhova, M. V., Bliese, P., Bossarte, R. M., Bromet, E. J., Fullerton, C. S., Gilman, S. E., Ivany, C., Lewandowski-Romps, L., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.110 · Cited by 163 · see citing works
A genome-wide association study of attempted suicide
Willour, V. L., Seifuddin, F., Mahon, P. B., Jancic, D., Pirooznia, M., Steele, J., Schweizer, B. W., Goes, F. S., Mondimore, F. M., MacKinnon, D. F., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.4 · Cited by 162 · see citing works
Genome-Wide Association Study of Suicide Attempts in Mood Disorder Patients
Perlis, R. H., Huang, J., Purcell, S., D, M. F. M., Rush, A. J., Sullivan, P. F., Hamilton, S. P., McMahon, F. J., Schulze, T. G., Potash, J. B., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.10040541 · Cited by 147 · see citing works
Yang, Q., Wu, H., Guo, C., & Fox, C. S. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20497 · Cited by 142 · see citing works
McCoy, T. H., Castro, V. M., Roberson, A. M., Snapper, L. A., & Perlis, R. H. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.2172 · Cited by 130 · see citing works
Suicidal behavior in twins: a replication
Roy, A., & Segal, N. L. (2001) · Journal of Affective Disorders · doi:10.1016/s0165-0327(00)00275-5 · Cited by 115 · see citing works
Biological risk factors for suicidal behaviors: a meta-analysis
Chang, B., Franklin, J. C., Ribeiro, J. D., Fox, K. R., Bentley, K. H., Kleiman, E. M., & Nock, M. K. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.165 · Cited by 115 · see citing works
Self-citationYang, J., Wray, N. R., & Visscher, P. M. (2009) · Genetic Epidemiology · doi:10.1002/gepi.20456 · Cited by 99 · see citing works
Genomewide association studies of suicide attempts in US soldiers
Stein, M. B., Ware, E. B., Mitchell, C. M., Chen, C., Borja, S. E., Cai, T., Dempsey, C. L., Fullerton, C. S., Gelernter, J. E., Heeringa, S. G., et al. (2017) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32594 · Cited by 62 · see citing works
Premature death among teenage mothers
Olausson, P. O., Haglund, B., Weitoft, G. R., et al. (2004) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2004.00248.x · Cited by 58 · see citing works
Genome-wide association studies of suicidal behaviors: a review
Sokolowski, M., Wasserman, J., & Wasserman, D. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.08.006 · Cited by 48 · see citing works
A genome-wide association study of suicide severity scores in bipolar disorder
Zai, C. C. H., Gonçalves, V. F., Tiwari, A. K., Taliun, S. A. G., Hosang, G. M., Luca, V. D., Shaikh, S. A., King, N. A., Chen, Q., Xu, W., et al. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.11.002 · Cited by 45 · see citing works
Age at first birth in women is genetically associated with increased risk of schizophrenia
Ni, G., Gratten, J., Wray, N. R., Lee, S., Ripke, S., Neale, B. M., Corvin, A. P., Walters, J., Farh, K.-H., Holmans, P., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-28160-z · Cited by 21 · see citing works
Genetic Associations with Subjective Well-Being Also Implicate Depression and NeuroticismPreprint
Okbay, A., Baselmans, B. M. L., Jan-emmanuel De Neve, A., Turley, P., Nivard, M. G., Fontana, M. A., Meddens, S. F. W., Linnér, R. K., Rietveld, C. A., Derringer, J. L., et al. (2015) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/032789 · Cited by 12 · see citing works
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Turecki, G., Brent, D. A., Gunnell, D., O’Connor, R. C., Oquendo, M. A., Pirkis, J., & Stanley, B. H. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0121-0 · Cited by 1,074 · see citing works
Mullins, N., Bigdeli, T. B., Børglum, A. D., Coleman, J. R. I., Demontis, D., Mehta, D., Power, R. A., Ripke, S., Stahl, E. A., Starnawska, A., et al. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.18080957 · Cited by 270 · see citing works
Psychiatric Symptoms Across the Menstrual Cycle in Adult Women: A Comprehensive Review
Handy, A. B., Greenfield, S. F., Yonkers, K. A., & Payne, L. A. (2022) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000329 · Cited by 153 · see citing works
Strawbridge, R. J., Ward, J., Ferguson, A., Graham, N., Shaw, R. J., Cullen, B., Pearsall, R., Lyall, L. M., Johnston, K. J. A., Niedzwiedz, C. L., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.02.005 · Cited by 112 · see citing works
Genome-Wide Association Study of Suicide Death and Polygenic Prediction of Clinical Antecedents
Docherty, A. R., Shabalin, A. A., DiBlasi, E., Monson, E., Mullins, N., Adkins, D. E., Bacanu, S.-A., Bakian, A. V., Crowell, S., Chen, D., et al. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2020.19101025 · Cited by 124 · see citing works
The molecular pathophysiology of depression and the new therapeutics
Tian, H., Hu, Z., Xu, J., & Wang, C. (2022) · MedComm · doi:10.1002/mco2.156 · Cited by 122 · see citing works
Genetic contributions to suicidal thoughts and behaviors
DiBlasi, E., Kang, J., & Docherty, A. R. (2021) · Psychological Medicine · doi:10.1017/s0033291721001720 · Cited by 83 · see citing works
Genetic aetiology of self-harm ideation and behaviour
Campos, A. I., Verweij, K. J. H., Statham, D. J., Madden, P. A. F., Maciejewski, D. F., Davis, K. A. S., John, A., Hotopf, M., Heath, A. C., Martin, N. G., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-66737-9 · Cited by 74 · see citing works
Genome-wide association study meta-analysis of suicide death and suicidal behavior
Li, Q. S., Shabalin, A. A., DiBlasi, E., Gopal, S., Canuso, C. M., FinnGen, I. S. G. C., Palotie, A., Drevets, W. C., Docherty, A. R., & Coon, H. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01828-9 · Cited by 68 · see citing works
Lee, D., Baek, J. H., Ha, K., Cho, E.-Y., Choi, Y., Yang, S.-Y., Kim, J. S., Cho, Y., Won, H.-H., & Hong, K. S. (2022) · International Journal of Bipolar Disorders · doi:10.1186/s40345-022-00251-x · Cited by 12 · see citing works
Salehi, M., Saeidi, M., Amanat, M., Barias, T., Anyeji, U., Alzein, O., & Gunturu, S. (2026) · Frontiers in Pediatrics · doi:10.3389/fped.2026.1738009
- Authors
- Ruderfer, D. M., Walsh, C. G., Aguirre, M. W., Tanigawa, Y., Ribeiro, J. D., Franklin, J. C., & Rivas, M. A.
- Affiliations
- Vanderbilt University (US)
- Vanderbilt University Medical Center (US)
- Stanford Medicine (US)
- Florida State University (US)
- Corresponding author
- Ruderfer, Douglas M.
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2019-01-04
- Volume
- 25
- Issue
- 10
- Pages
- 2422-2430
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC6609505
- OpenAlex
- W2952226016
- Cited by
- 134
- References
- 45
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 19 · 2023: 24 · 2022: 16 · 2021: 22 · 2020: 17 · 2019: 8 · 2018: 2
- FWCI
- 18.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Vanderbilt University (UL1 RR024975, UL1‐TR000445, U01HG006378)
- Vanderbilt University Medical Center (U19HL065962, U01HG006378, RC2GM092618, UL1TR000445, S10RR025141, UL1 RR024975, P50GM115305, UL1 TR002243, R01NS032830, R01HD074711, U01HG004798)
- Georgia Clinical and Translational Science Alliance (UL1 RR024975, U19HL065962, UL1TR002243, UL1TR000445, RC2GM092618, U01HG006378, P50GM115305, R01NS032830, U01HG004798, R01HD074711)
- National Institutes of Health (UL1TR000445, UL1TR002243)
- Medical Research Council (MC_PC_17228)
- National Heart, Lung, and Blood Institute (U19HL065962)
- National Human Genome Research Institute (U01HG006378, U01HG004798)
- National Institute of General Medical Sciences (P50GM115305, R25GM062459, RC2GM092618)
- National Institute of Neurological Disorders and Stroke (R01NS032830)
- U.S. National Library of Medicine (T15LM007033)
- National Center for Research Resources (S10RR025141, UL1RR024975)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD074711)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- suicide attempts, heritability, common genetic variants, polygenic risk score, genetic correlation, insomnia, mental illness, electronic health records, UK Biobank, binary phenotypes
- MeSH terms
- Machine Learning, Female, United Kingdom, Health Surveys, Humans, Male, Mental Health, Phenotype, Probability, Risk Factors, Suicide, Attempted, Tennessee, Biological Specimen Banks, White People, Genome-Wide Association Study, Electronic Health Records, Suicidal Ideation
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