Exploring the genetic overlap of suicide-related behaviors and substance use disorders.
| Title: | Exploring the genetic overlap of suicide-related behaviors and substance use disorders. |
|---|---|
| Authors: | Colbert SMC; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hatoum AS; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Shabalin A; Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, Utah, USA.; Li QS; Neuroscience and JRD Data Science, Janssen Research & Development, LLC, Titusville, New Jersey, USA.; Coon H; Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, Utah, USA.; Nelson EC; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Agrawal A; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Docherty AR; Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, Utah, USA.; Johnson EC; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. |
| Source: | American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics [Am J Med Genet B Neuropsychiatr Genet] 2021 Dec; Vol. 186 (8), pp. 445-455. Date of Electronic Publication: 2021 Nov 25. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101235742 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-485X (Electronic) Linking ISSN: 15524841 NLM ISO Abbreviation: Am J Med Genet B Neuropsychiatr Genet Subsets: MEDLINE |
| Imprint Name(s): | Publication: Hoboken, N.J. : Wiley-Blackwell; Original Publication: Hoboken, N.J. : Wiley-Liss, c2003- |
| MeSH Terms: | Substance-Related Disorders*/genetics ; Genome-Wide Association Study* ; Suicide, Attempted*; Genomics ; Humans ; Linkage Disequilibrium ; Mendelian Randomization Analysis |
| Abstract: | Suicide-related behaviors are heterogeneous and transdiagnostic, and may demonstrate varying levels of genetic overlap with different substance use disorders (SUDs). We used linkage disequilibrium score regression, genomic structural equation models, and Mendelian randomization 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, the Fagerström test for nicotine dependence, cannabis use disorder, and opioid use disorder (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). Suicide-related behaviors were significantly genetically correlated with each other and each SUD, but there was little evidence of causal relationships between the traits. Simultaneously correlating a common SUD factor with each specific suicide indicator while controlling for depression and risk tolerance revealed significant, positive genetic correlations between the SUD factor and suicide-related behaviors (rg = 0.26-0.45, SE = 0.08-0.09). In the model, depression's association with suicide death (β = 0.42, SE = 0.06) was weaker compared to ever-self harmed and suicide attempt (β = 0.58, SE = 0.05 and β = 0.50, SE = 0.06, respectively). We identify a general level of genetic overlap between SUDs and suicide-related behaviors, which is independent of depression and risk tolerance. Additionally, our findings suggest that genetic and behavioral contributions to suicide death may somewhat differ from nonlethal suicide-related behaviors.; (© 2021 Wiley Periodicals LLC.) |
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| Grant Information: | K02 DA032573 United States DA NIDA NIH HHS; UL1 TR002538 United States TR NCATS NIH HHS; R01 MH123489 United States MH NIMH NIH HHS; T32 DA007261 United States DA NIDA NIH HHS; U01 MH109532 United States MH NIMH NIH HHS; R01 MH122412 United States MH NIMH NIH HHS; R01 MH123619 United States MH NIMH NIH HHS |
| Contributed Indexing: | Keywords: genetic overlap; genome-wide association studies; genomic structural equation models; substance use disorders; suicide |
| Entry Date(s): | Date Created: 20211125 Date Completed: 20220114 Latest Revision: 20240809 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8692412 |
| DOI: | 10.1002/ajmg.b.32880 |
| PMID: | 34821019 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.