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Shared genetic and environmental etiology between substance use disorders and suicidal behavior

Published online by Cambridge University Press:  12 November 2021

Alexis C. Edwards*
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
Henrik Ohlsson
Center for Primary Health Care Research, Lund University, Malmö, Sweden
Séverine Lannoy
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
Mallory Stephenson
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
Casey Crump
Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Jan Sundquist
Center for Primary Health Care Research, Lund University, Malmö, Sweden Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Kristina Sundquist
Center for Primary Health Care Research, Lund University, Malmö, Sweden Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Kenneth S. Kendler
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
Author for correspondence: Alexis C. Edwards, E-mail:



Previous studies have demonstrated substantial associations between substance use disorders (SUD) and suicidal behavior. The current study empirically assesses the extent to which shared genetic and/or environmental factors contribute to associations between alcohol use disorders (AUD) or drug use disorders (DUD) and suicidal behavior, including attempts and death.


The authors used Swedish national registry data, including medical, pharmacy, criminal, and death registrations, for a large cohort of twins, full siblings, and half siblings (N = 1 314 990) born 1960–1980 and followed through 2017. They conducted twin-sibling modeling of suicide attempt (SA) or suicide death (SD) with AUD and DUD to estimate genetic and environmental correlations between outcomes. Analyses were stratified by sex.


Genetic correlations between SA and SUD ranged from rA = 0.60–0.88; corresponding shared environmental correlations were rC = 0.42–0.89 but accounted for little overall variance; and unique environmental correlations were rE = 0.42–0.57. When replacing attempt with SD, genetic and shared environmental correlations with AUD and DUD were comparable (rA = 0.48–0.72, rC = 0.92–1.00), but were attenuated for unique environmental factors (rE = −0.01 to 0.31).


These findings indicate that shared genetic and unique environmental factors contribute to comorbidity of suicidal behavior and SUD, in conjunction with previously reported causal associations. Thus, each outcome should be considered an indicator of risk for the others. Opportunities for joint prevention and intervention, while limited by the polygenic nature of these outcomes, may be feasible considering moderate environmental correlations between SA and SUD.

Original Article
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Joint senior authors.


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