A genetically informed study on the association of cannabis, alcohol, and tobacco smoking with suicide attempt.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
20
10
2019
accepted:
12
05
2020
revised:
06
05
2020
pubmed:
9
6
2020
medline:
1
2
2022
entrez:
9
6
2020
Statut:
ppublish
Résumé
Use of substances such as cannabis, alcohol, and tobacco, has been associated with increased risk of suicide attempt in several observational studies. However, establishing whether these associations are causal is challenging when using observational designs. To evaluate the potential causal contributions of cannabis use, alcohol use, and tobacco smoking to suicide attempt, we applied two-sample Mendelian randomization, an instrumental variable approach using single-nucleotide polymorphisms (SNPs) as instrumental variables for three exposures: lifetime cannabis use (yes/no; 42 instrument SNPs; GWAS sample size [N] = 162,082), alcohol use (drinks-per-week; 53 instrument SNPs; N = 941,280), and tobacco smoking (initiation, yes/no; 156 instrument SNPs; N = 1,232,091; heaviness; 27 instrument SNPs; N = 337,334). The main outcome was suicide attempt measured from hospital records (N = 50,264). All data come from publicly available summary statistics of genome-wide association studies of participants of European ancestry. We found evidence supporting a possible causal role of cannabis (OR = 1.18; 95% CI = 1.01-1.37, P = 0.032), alcohol (OR = 1.95; 95% CI = 1.15-3.32, P = 0.013), and smoking (initiation, OR = 1.90; 95% CI = 1.54-2.34, P < 0.001; heaviness, OR = 2.13; 95% CI = 1.13-3.99; P = 0.019) on suicide attempt. Using multivariable Mendelian randomization, we found that only cannabis showed a direct pathway to suicide attempt (P = 0.001), suggesting that the effect of alcohol and smoking was mediated by the other substance use phenotypes. No evidence was found for reverse causation, i.e., associations of suicide attempt on cannabis (P = 0.483), alcohol (P = 0.234), smoking initiation (P = 0.144), and heaviness (P = 0.601). In conclusion, evidence from this quasi-experimental study based on genetic data from large-scale GWASs are consistent with a causal role of cannabis, alcohol, and tobacco smoking on suicide attempt.
Identifiants
pubmed: 32507850
doi: 10.1038/s41380-020-0785-6
pii: 10.1038/s41380-020-0785-6
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5061-5070Subventions
Organisme : CIHR
ID : FDN148374
Pays : Canada
Organisme : CIHR
ID : EGM141899
Pays : Canada
Organisme : CIHR
ID : PJT-148551
Pays : Canada
Informations de copyright
© 2020. The Author(s), under exclusive licence to Springer Nature Limited.
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