Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality
Open Access
- 11 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Translational Psychiatry
- Vol. 11 (1), 1-11
- https://doi.org/10.1038/s41398-020-01153-1
Abstract
Substance dependence diagnoses (SDs) are important risk factors for suicidality. We investigated the associations of multiple SDs with different suicidality outcomes, testing how genetic background moderates these associations. The Yale-Penn cohort (N = 15,557) was recruited to investigate the genetics of SDs. The Army STARRS (Study to Assess Risk and Resilience in Servicemembers) cohort (N = 11,236) was recruited to evaluate mental health risk and resilience among Army personnel. We applied multivariate logistic regression to investigate the associations of SDs with suicidality and, in the Yale-Penn cohort, we used the structured linear mixed model (StructLMM) to study multivariate gene–environment interactions. In Yale-Penn, lifetime polysubstance dependence was strongly associated with lifetime suicidality: having five SDs showed an association with suicidality, from odds ratio (OR) = 6.77 (95% confidence interval, CI = 5.74–7.99) for suicidal ideation (SI) to OR = 3.61 (95% CI = 2.7–4.86) for suicide attempt (SA). In Army STARRS, having multiple substance use disorders for alcohol and/or drugs was associated with increased suicidality ranging from OR = 2.88 (95% CI = 2.6–3.19) for SI to OR = 3.92 (95% CI = 3.19–4.81) for SA. In Yale-Penn, we identified multivariate gene–environment interactions (Bayes factors, BF > 0) of SI with respect to a gene cluster on chromosome 16 (LCAT, p = 1.82 × 10–7; TSNAXIP1, p = 2.13 × 10−7; CENPT, p = 2.32 × 10−7; PARD6A, p = 5.57 × 10−7) for opioid dependence (BF = 12.2), cocaine dependence (BF = 12.1), nicotine dependence (BF = 9.2), and polysubstance dependence (BF = 2.1). Comorbidity of multiple SDs is a significant associated with suicidality and heritability of suicidality is partially moderated by multivariate gene interactions.Funding Information
- U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse
- American Foundation for Suicide Prevention
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health
- U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse
- U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism
This publication has 52 references indexed in Scilit:
- Genome-wide association studies identify polygenic effects for completed suicide in the Japanese populationNeuropsychopharmacology, 2019
- GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk ScoresAmerican Journal of Psychiatry, 2019
- Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicideEBioMedicine, 2019
- Correlates of Opioid Use Disorders among People with Severe Mental Illness in the United StatesSubstance Use & Misuse, 2019
- Genetic associations with suicide attempt severity and genetic overlap with major depressionTranslational Psychiatry, 2019
- Genomewide association studies of suicide attempts in US soldiersNeuropsychiatric Genetics, Part B of the American Journal of Medical Genetics (AJMG), 2017
- Substance use disorders and the risk of suicide mortality among men and women in the US Veterans Health AdministrationAddiction, 2017
- The Interplay Between Risky Sexual Behaviors and Alcohol Dependence: Genome-Wide Association and Neuroimaging Support for LHPP as a Risk GeneNeuropsychopharmacology, 2016
- Addiction and suicide: A reviewThe American Journal on Addictions, 2015
- Gene–Environment Interaction: Definitions and Study DesignPreventive Medicine, 1996