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Genetic liability to suicide attempt, suicide death, and psychiatric and substance use disorders on the risk for suicide attempt and suicide death: a Swedish national study

Published online by Cambridge University Press:  02 September 2021

Kenneth S. Kendler Open the ORCID record for Kenneth S. Kendler [Opens in a new window] ,
Henrik Ohlsson ,
Eve K. Mościcki ,
Jan Sundquist ,
Alexis C. Edwards  and
Kristina Sundquist
Kenneth S. Kendler*
Affiliation:
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
Henrik Ohlsson
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden
Eve K. Mościcki
Affiliation:
Private Consultant, Washington, DC, USA
Jan Sundquist
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA
Alexis C. Edwards
Affiliation:
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
Kristina Sundquist
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA
*
Author for correspondence: Kenneth S. Kendler, E-mail: Kenneth.Kendler@vcuhealth.org
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Abstract

Background

How does genetic liability to suicide attempt (SA), suicide death (SD), major depression (MD), bipolar disorder (BD), schizophrenia (SZ), alcohol use disorder (AUD), and drug use disorder (DUD) impact on risk for SA and SD?

Methods

In the Swedish general population born 1932–1995 and followed through 2017 (n = 7 661 519), we calculate family genetic risk scores (FGRS) for SA, SD, MD, BD, SZ, AUD, and DUD. Registration for SA and SD was assessed from Swedish national registers.

Results

In univariate and multivariate models predicting SA, FGRS were highest for SA, AUD, DUD, and MD. In univariate models predicting SD, the strongest FGRS were AUD, DUD, SA, and SD. In multivariate models, the FGRS for SA and AUD were higher in predicting SA while the FGRS for SD, BD, and SZ were higher in predicting SD. Higher FGRS for all disorders significantly predicted both younger age at first SA and frequency of attempts. For SD, higher FGRS for MD, AUD, and SD predicted later age at SD. Mediation of FGRS effects on SA and SD was more pronounced for SD than SA, strongest for AUD, DUD, and SZ FGRS and weakest for MD.

Conclusions

FGRS for both SA and SD and for our five psychiatric disorders impact on risk for SA and SD in a complex manner. While some of the impact of genetic risk factors for psychiatric disorders on risk for SA and SD is mediated through developing the disorders, these risks also predispose directly to suicidal behaviors.

Keywords

Suicide attemptSuicide DeathGeneticsPsychiatric and Substance Use Disorders
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 4 , March 2023 , pp. 1639 - 1648
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

Shared senior author.

References

Arsenault-Lapierre, G., Kim, C., & Turecki, G. (2004). Psychiatric diagnoses in 3275 suicides: A meta-analysis. BMC Psychiatry, 4(1), 37.CrossRefGoogle Scholar
Baldessarini, R. J., & Hennen, J. (2004). Genetics of suicide: An overview. Harvard Review of Psychiatry, 12(1), 1–13, doi:PCYX02B8G12YGJCB [pii].CrossRefGoogle ScholarPubMed
Ballard, E. D., Cui, L., Vandeleur, C., Castelao, E., Zarate, C. A., Preisig, M., & Merikangas, K. R. (2019). Familial aggregation and coaggregation of suicide attempts and comorbid mental disorders in adults. JAMA Psychiatry, 76(8), 826–833.CrossRefGoogle ScholarPubMed
Brent, D. A., & Melhem, N. (2008). Familial transmission of suicidal behavior. Psychiatric Clinics of North America, 31(2), 157–177, doi:S0193-953X(08)00025-7 [pii]; doi:10.1016/j.psc.2008.02.001 [doi].CrossRefGoogle ScholarPubMed
Cavanagh, J. T., Carson, A. J., Sharpe, M., & Lawrie, S. M. (2003). Psychological autopsy studies of suicide: A systematic review. Psychological Medicine, 33(3), 395–405.CrossRefGoogle Scholar
Docherty, A. R., Shabalin, A. A., DiBlasi, E., Monson, E., Mullins, N., Adkins, D. E., … Chen, D. (2020). Genome-wide association study of suicide death and polygenic prediction of clinical antecedents. American Journal of Psychiatry, 177(10), 917–927.CrossRefGoogle ScholarPubMed
Edwards, A. C., Ohlsson, H., Moscicki, E. K., Crump, C., Sundquist, J., Lichtenstein, P., … Sundquist, K. (In Press). On the genetic and environmental relationship between suicide attempt and death by suicide. American Journal of Psychiatry, In press.Google Scholar
Edwards, A. C., Ohlsson, H., Sundquist, J., Sundquist, K., & Kendler, K. S. (2020). Alcohol use disorder and risk of suicide in a Swedish population-based cohort. American Journal of Psychiatry, 177(7), 627–634. doi: 10.1176/appi.ajp.2019.19070673CrossRefGoogle Scholar
Ekholm, B., Ekholm, A., Adolfsson, R., Vares, M., Osby, U., Sedvall, G. C., & Jonsson, E. G. (2005). Evaluation of diagnostic procedures in Swedish patients with schizophrenia and related psychoses. Nordic Journal of Psychiatry, 59(1), 457–464.CrossRefGoogle ScholarPubMed
Forman, E. M., Berk, M. S., Henriques, G. R., Brown, G. K., & Beck, A. T. (2004). History of multiple suicide attempts as a behavioral marker of severe psychopathology. American Journal of Psychiatry, 161(3), 437–443.CrossRefGoogle Scholar
Fu, Q., Heath, A. C., Bucholz, K. K., Nelson, E. C., Glowinski, A. L., Goldberg, J., … Eisen, S. A. (2002). A twin study of genetic and environmental influences on suicidality in men. Psychological Medicine, 32(1), 11–24. doi: 10.1017/s0033291701004846CrossRefGoogle ScholarPubMed
Glowinski, A. L., Bucholz, K. K., Nelson, E. C., Fu, Q., Madden, P. A., Reich, W., & Heath, A. C. (2001). Suicide attempts in an adolescent female twin sample. Journal of the American Academy of Child & Adolescent Psychiatry, 40(11), 1300–1307.CrossRefGoogle Scholar
Harris, E. C., & Barraclough, B. (1997). Suicide as an outcome for mental disorders. A meta-analysis. British Journal of Psychiatry, 170(3), 205–228.CrossRefGoogle ScholarPubMed
Hujoel, M. L., Gazal, S., Loh, P.-R., Patterson, N., & Price, A. L. (2020). Liability threshold modeling of case–control status and family history of disease increases association power. Nature Genetics, 52(5), 541–547.CrossRefGoogle ScholarPubMed
Jamison, E. C., Bol, K. A., & Mintz, S. N. (2019). Analysis of the effects on time between divorce decree and suicide. Crisis, 40, 309–316.CrossRefGoogle ScholarPubMed
Kaplan, M. S., McFarland, B. H., Huguet, N., Conner, K., Caetano, R., Giesbrecht, N., & Nolte, K. B. (2013). Acute alcohol intoxication and suicide: A gender-stratified analysis of the National Violent Death Reporting System. Injury Prevention, 19(1), 38–43.CrossRefGoogle ScholarPubMed
Kendler, K. S., Ji, J., Edwards, A. C., Ohlsson, H., Sundquist, J., & Sundquist, K. (2015). An extended Swedish national adoption study of alcohol use disorder. JAMA Psychiatry, 72(3), 211–218, doi:2088151 [pii]; doi:10.1001/jamapsychiatry.2014.2138 [doi].CrossRefGoogle ScholarPubMed
Kendler, K. S., Lonn, S. L., Salvatore, J., Sundquist, J., & Sundquist, K. (2017). Divorce and the onset of alcohol use disorder: A Swedish population-based longitudinal cohort and co-relative study. American Journal of Psychiatry, 174(5), 451–458. doi: 10.1176/appi.ajp.2016.16050589 [doi].CrossRefGoogle ScholarPubMed
Kendler, K. S., Ohlsson, H., Karriker-Jaffe, K. J., Sundquist, J., & Sundquist, K. (2016). Social and economic consequences of alcohol use disorder: A longitudinal cohort and co-relative analysis. Psychological Medicine, 47(5), 925–935. doi:S0033291716003032 [pii]; doi:10.1017/S0033291716003032 [doi].CrossRefGoogle ScholarPubMed
Kendler, K. S., Ohlsson, H., Lichtenstein, P., Sundquist, J., & Sundquist, K. (2018). The genetic epidemiology of treated major depression in Sweden. American Journal of Psychiatry, 175(11), 1137–1144. doi: 10.1176/appi.ajp.2018.17111251 [doi].CrossRefGoogle ScholarPubMed
Kendler, K. S., Ohlsson, H., Sundquist, J., & Sundquist, K. (2021a). Family genetic risk scores and the genetic architecture of major affective and psychotic disorders in a Swedish national sample. JAMA Psychiatry, 78, 735–743. 10.1001/jamapsychiatry.2021.0336.CrossRefGoogle Scholar
Kendler, K. S., Ohlsson, H., Sundquist, J., & Sundquist, K. (2021b). The patterns of family genetic risk scores for eleven major psychiatric and substance use disorders in a Swedish national sample. Translational Psychiatry, 11(1), 1–8.CrossRefGoogle Scholar
Kendler, K. S., Ohlsson, H., Sundquist, J., Sundquist, K., & Edwards, A. C. (2020). The sources of parent-child transmission of risk for suicide attempt and deaths by suicide in Swedish national samples. American Journal of Psychiatry, 177(10), 928–935. doi: 10.1176/appi.ajp.2020.20010017CrossRefGoogle ScholarPubMed
Kendler, K. S., Sundquist, K., Ohlsson, H., Palmer, K., Maes, H., Winkleby, M. A., & Sundquist, J. (2012). Genetic and familial environmental influences on the risk for drug abuse: A national Swedish adoption study. Archive of General Psychiatry, 69(7), 690–697. doi: 10.1001/archgenpsychiatry.2011.2112CrossRefGoogle ScholarPubMed
Kessler, R. C., Berglund, P., Borges, G., Nock, M., & Wang, P. S. (2005). Trends in suicide ideation, plans, gestures, and attempts in the United States, 1990–1992 to 2001–2003. JAMA, 293(20), 2487–2495.CrossRefGoogle ScholarPubMed
Lichtenstein, P., Bjork, C., Hultman, C. M., Scolnick, E., Sklar, P., & Sullivan, P. F. (2006). Recurrence risks for schizophrenia in a Swedish national cohort. Psychological Medicine, 36(10), 1417–1425. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16863597.CrossRefGoogle Scholar
Lorant, V., Kunst, A. E., Huisman, M., Costa, G., & Mackenbach, J. (2005). Socio-economic inequalities in suicide: A European comparative study. The British Journal of Psychiatry, 187(1), 49–54.CrossRefGoogle ScholarPubMed
Mann, J. J., & Rizk, M. M. (2020). A brain-centric model of suicidal behavior. American Journal of Psychiatry, 177(10), 902–916.CrossRefGoogle ScholarPubMed
McGirr, A., Renaud, J., Bureau, A., Seguin, M., Lesage, A., & Turecki, G. (2008). Impulsive-aggressive behaviours and completed suicide across the life cycle: A predisposition for younger age of suicide. Psychological Medicine, 38(3), 407.CrossRefGoogle ScholarPubMed
Mullins, N., Kang, J., Campos, A. I., Coleman, J. R., Edwards, A. C., Galfalvy, H., … Starnawska, A. (2020). Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors. medRxiv.CrossRefGoogle Scholar
Muthén, L. K., & Muthén, B. O. (2015). Mplus user's guide: 1998–2015 (7th ed.). Los Angeles, CA: Muthén & Muthén.Google Scholar
National Board of Forensic Medicine (2018). Rättsmedicinalverket Årsredovisning 2018 Ref Dnr X18-91302 (National Board of Forensic Medicine Annual Report 2018). Retrieved from https://www.rmv.se/wp-content/uploads/Slutlig-%C3%85R-2018-R%C3%A4ttsmedicinalverket-2019-02-22.pdf.Google Scholar
Nock, M. K., Hwang, I., Sampson, N., Kessler, R. C., Angermeyer, M., Beautrais, A., … De Girolamo, G. (2009). Cross-national analysis of the associations among mental disorders and suicidal behavior: Findings from the WHO World Mental Health Surveys. PLoS Medicine, 6(8), e1000123.CrossRefGoogle ScholarPubMed
Pedersen, N. L., & Fiske, A. (2010). Genetic influences on suicide and nonfatal suicidal behavior: Twin study findings. European Psychiatry, 25(5), 264–267. doi:S0924-9338(10)00048-9 [pii]; doi:10.1016/j.eurpsy.2009.12.008 [doi].CrossRefGoogle ScholarPubMed
Petersen, L., Sorensen, T. I., Andersen, P. K., Mortensen, P. B., & Hawton, K. (2013). Genetic and familial environmental effects on suicide – an adoption study of siblings. PLoS ONE, 8(10), e77973. doi: 10.1371/journal.pone.0077973CrossRefGoogle ScholarPubMed
Petersen, L., Sorensen, T. I., Kragh, A. P., Mortensen, P. B., & Hawton, K. (2014). Genetic and familial environmental effects on suicide attempts: A study of Danish adoptees and their biological and adoptive siblings. Journal of Affective Disorders, 155, 273–277. doi:S0165-0327(13)00823-9 [pii]; doi:10.1016/j.jad.2013.11.012 [doi].CrossRefGoogle ScholarPubMed
Qin, P., Agerbo, E., & Mortensen, P. B. (2002). Suicide risk in relation to family history of completed suicide and psychiatric disorders: A nested case-control study based on longitudinal registers. The Lancet, 360(9340), 1126–1130.CrossRefGoogle ScholarPubMed
Rich, C. L., Young, D., & Fowler, R. C. (1986). San Diego suicide study: I. Young vs old subjects. Archives of General Psychiatry, 43(6), 577–582.CrossRefGoogle Scholar
Roškar, S., Podlesek, A., Kuzmanić, M., Demšar, L. O., Zaletel, M., & Marušič, A. (2011). Suicide risk and its relationship to change in marital status. Crisis, 32, 24–30.CrossRefGoogle ScholarPubMed
Rosoff, D. B., Kaminsky, Z. A., McIntosh, A. M., Smith, G. D., & Lohoff, F. W. (2020). Educational attainment reduces the risk of suicide attempt among individuals with and without psychiatric disorders independent of cognition: A bidirectional and multivariable Mendelian randomization study with more than 815 000 participants. Translational Psychiatry, 10(1), 1–15.CrossRefGoogle ScholarPubMed
SAS Institute, I. (2012). SAS/STAT® online documentation, version 9.4. Cary, NC: SAS Institute, Inc.Google Scholar
Schulsinger, F., Kety, S. S., Rosenthal, D., & Wender, P. H. (1979). A family study of suicide. In Schou, M., & Stromgren, E. (Eds.), Origin, prevention and treatment of affective disorders (pp. 277–287). New York: Academic Press.Google Scholar
Sellgren, C., Landen, M., Lichtenstein, P., Hultman, C. M., & Langstrom, N. (2011). Validity of bipolar disorder hospital discharge diagnoses: File review and multiple register linkage in Sweden. Acta Psychiatrica Scandinavica, 124(6), 447–453. doi: 10.1111/j.1600-0447.2011.01747.x [doi].CrossRefGoogle ScholarPubMed
Smoller, J. W., Andreassen, O. A., Edenberg, H. J., Faraone, S. V., Glatt, S. J., & Kendler, K. S. (2019). Psychiatric genetics and the structure of psychopathology. Molecular Psychiatry, 24(3), 409–420. doi: 10.1038/s41380-017-0010-4CrossRefGoogle ScholarPubMed
Statistics Sweden (2004). Statistics Sweden: causes of death 2002. Retrieved from http://www.scb.se/en/.Google Scholar
Sundquist, J., Ohlsson, H., Sundquist, K., & Kendler, K. S. (2017). Common adult psychiatric disorders in Swedish primary care (where most mental health patients are treated). BMC Psychiatry, 17(1), 235.CrossRefGoogle ScholarPubMed
Tidemalm, D., Haglund, A., Karanti, A., Landén, M., & Runeson, B. (2014). Attempted suicide in bipolar disorder: Risk factors in a cohort of 6086 patients. PLoS ONE, 9(4), e94097.CrossRefGoogle Scholar
Tidemalm, D., Långström, N., Lichtenstein, P., & Runeson, B. (2008). Risk of suicide after suicide attempt according to coexisting psychiatric disorder: Swedish cohort study with long term follow-up. BMJ, 337, a2205.CrossRefGoogle ScholarPubMed
Tidemalm, D., Runeson, B., Waern, M., Frisell, T., Carlstrom, E., Lichtenstein, P., & Langstrom, N. (2011). Familial clustering of suicide risk: A total population study of 11.4 million individuals. Psychological Medicine, 41(12), 2527–2534, doi:S0033291711000833 [pii]; doi:10.1017/S0033291711000833 [doi].CrossRefGoogle Scholar
Tollefsen, I. M., Hem, E., & Ekeberg, O. (2012). The reliability of suicide statistics: A systematic review. BMC Psychiatry, 12, 9. doi: 10.1186/1471-244x-12-9CrossRefGoogle ScholarPubMed
Verhulst, B., Neale, M. C., & Kendler, K. S. (2015). The heritability of alcohol use disorders: A meta-analysis of twin and adoption studies. Psychological Medicine, 45(5), 1061–1072. doi:S0033291714002165 [pii]; doi:10.1017/S0033291714002165 [doi].CrossRefGoogle ScholarPubMed
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