Exploring the genetic overlap of suicide-related behaviors and substance use disorders

Abstract

Background: Suicide-related behaviors are heterogeneous and transdiagnostic, and may demonstrate varying levels of genetic overlap with different substance use disorders (SUDs). Methods: We used linkage disequilibrium score regression and genomic structural equation models to examine the genetic relationships between several SUDs and suicide-related behaviors. Our analyses incorporated summary statistics from the largest genome-wide association studies (GWAS) of problematic alcohol use (PAU), the Fagerstrom Test for Nicotine Dependence (FTND), cannabis use disorder (CUD), and opioid use disorder (OUD; Ns ranging from 46,213-435,563) and GWAS of ever self-harmed, suicide attempt, and suicide death (Ns ranging from 18,223-117,733). We also accounted for genetic liability to depression (N=500,199) and risk tolerance (N=315,894). Results: Ever self-harmed correlated most strongly with CUD (rg=0.60) and suicide death correlated most strongly with OUD (rg=0.53). Suicide attempt correlated similarly with all SUDs. Simultaneously correlating a common SUD factor with each specific suicide indicator while controlling for depression and risk tolerance revealed significant, positive genetic correlations between all SUDs and suicide-related behaviors (rg=0.26-0.46). Discussion: Our findings suggest that genetic and behavioral contributions to suicide death may somewhat differ from non-lethal suicide-related behaviors. Additionally, we identify a general level of genetic overlap between SUDs and suicide-related behaviors which is independent of depression and risk tolerance.

Sibling Alcohol Use Disorder Is Associated With Increased Risk for Suicide Attempt

“…In an independent ongoing effort that employs twin-sibling biometric models, our preliminary findings suggest moderate to substantial genetic and environmental correlations (genetic correlation [rA] ≈ 0.6–0.7; shared environmental correlation [rC] ≈ 0.7–0.9; nonshared environmental correlation [rE] ≈ 0.5–0.6; Edwards et al, 2021). These results parallel findings from a recent molecular genetic study, which reported a genetic correlation of .52 between suicide attempt and problematic alcohol use (Colbert et al, 2021); this molecular approach precludes estimating environmental correlations.…”

Genetics and epigenetics of self‐injurious thoughts and behaviors: Systematic review of the suicide literature and methodological considerations

“…Six studies performed Mendelian randomizations focused on candidate genes involved with substance use disorders, insomnia, atopic dermatitis, inflammation, and blood lipids. There was no evidence that genes involved in substance use disorders contribute to self‐harm, SA, or SD (Colbert et al, 2021). There was also no evidence that genes involved in atopic dermatitis contribute to SI or SA (Qi & Li, 2022).…”

Genetic propensity for risky behavior and depression and risk of lifetime suicide attempt among urban African Americans in adolescence and young adulthood

“…Indeed, a recent GWAS conducted in European ancestry samples identified numerous genetic loci implicated in four risky behaviors, including number of sexual partners, drinks per week, lifetime history of smoking, and automobile speeding propensity (Karlson Línner et al, 2019). In terms of the genetic association between risky behaviors and suicide attempt, research has observed moderate positive genetic correlations between risk tolerance (i.e., one's preference for taking risks) and suicide attempts (r g = 0.33) (Colbert et al, 2021). Similarly, using a twin design, other research has indicated that close to 40% of the genetic variation in suicidal behaviors was shared with impulsive-aggressive behaviors (Orri et al, 2020).…”