Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality.

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.

SUBMITTER: Polimanti R 

PROVIDER: S-EPMC7801457 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature