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

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.

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Shared Genetic Vulnerability for Disordered Gambling and Alcohol Use Disorder in Men and Women: Evidence from a National Community-Based Australian Twin Study

Twin Research and Human Genetics ◽

10.1017/thg.2013.11 ◽

2013 ◽

Vol 16 (2) ◽

pp. 525-534 ◽

Cited By ~ 50

Author(s):

Wendy S. Slutske ◽

Jarrod M. Ellingson ◽

Leah S. Richmond-Rakerd ◽

Gu Zhu ◽

Nicholas G. Martin

Keyword(s):

Substance Use ◽

Substance Use Disorders ◽

Alcohol Use Disorder ◽

Disordered Gambling ◽

Community Based ◽

Men And Women ◽

National Community ◽

Dsm 5 ◽

Genetic Overlap ◽

Shared Genetic

Disordered gambling (DG) will soon be included along with the substance use disorders in a revised diagnostic category of the Diagnostic and Statistical Manual of Mental Disorders DSM-5 called ‘Substance Use and Addictive Disorders’. This was premised in part on the common etiologies of DG and the substance use disorders. Using data from the national community-based Australian Twin Registry, we used biometric model fitting to examine the extent to which the genetic liabilities for DG and alcohol use disorder (AUD) were shared, and whether this differed for men and women. The effect of using categorical versus dimensional DG and AUD phenotypes was explored, as was the effect of using diagnoses based on the DSM-IV and the proposed DSM-5 diagnostic criteria. The genetic correlations between DG and AUD ranged from 0.29 to 0.44. There was a significantly larger genetic correlation between DG and AUD among men than women when using dimensional phenotypes. Overall, about one-half to two-thirds of the association between DG and AUD was due to a shared genetic vulnerability. This study represents one of the few empirical demonstrations of an overlap in the genetic risk for DG and another substance-related addictive disorder. More research is needed on the genetic overlap between DG and other substance use disorders, as well as the genetic overlap between DG and other (non-substance-related) psychiatric disorders.

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