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

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... 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.