Exploring the genetic overlap of suicide-related behaviors and substance use disorders
© 2021 Wiley Periodicals LLC..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:186 |
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| Enthalten in: |
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics - 186(2021), 8 vom: 19. Dez., Seite 445-455 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Colbert, Sarah M C [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.01.2022 Date Revised 04.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/ajmg.b.32880 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a genetic overlap | |
| 650 | 4 | |a genome-wide association studies | |
| 650 | 4 | |a genomic structural equation models | |
| 650 | 4 | |a substance use disorders | |
| 650 | 4 | |a suicide | |
| 700 | 1 | |a Hatoum, Alexander S |e verfasserin |4 aut | |
| 700 | 1 | |a Shabalin, Andrey |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Qingqin S |e verfasserin |4 aut | |
| 700 | 1 | |a Coon, Hilary |e verfasserin |4 aut | |
| 700 | 1 | |a Nelson, Elliot C |e verfasserin |4 aut | |
| 700 | 1 | |a Agrawal, Arpana |e verfasserin |4 aut | |
| 700 | 1 | |a Docherty, Anna R |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Emma C |e verfasserin |4 aut | |
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