Journal
NATURE NEUROSCIENCE
Volume 21, Issue 9, Pages 1161-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41593-018-0206-1
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Funding
- European Research Council (Beyond the Genetics of Addiction) [ERC-284167]
- Foundation Volksbond Rotterdam
- US National Institutes of Health, National Institute on Drug Abuse [R00DA023549]
- Netherlands Organization for Scientific Research (NWO) [446-16009]
- Australian Research Council Fellowship
- Netherlands Organization for Scientific Research [NWO 480-05-003]
- Royal Netherlands Academy of Science Professor Award [PAH/6635]
- NWO Exact Sciences
- NIDA
- NIMH [MH109532]
- NIAAA [U01AA008401]
- Peter Boris Chair in Addictions Research
- Frontiers of Innovation Scholars Program (FISP) [3-P3029]
- Interdisciplinary Research Fellowship in NeuroAIDS (IRFN) [MH081482]
- pilot award [DA037844]
- European Union through the European Regional Development Fund [2014-2020.4.01.15-0012]
- European Union's Horizon 2020 Research and Innovation Programme [692065, 692145]
- Academy of Finland [263278, 292782]
- Instituto de Salud Carlos III, Spain [CP09/00119, CPII15/00023]
- MRC [MC_UU_00011/7, MC_UU_12015/2] Funding Source: UKRI
- Academy of Finland (AKA) [292782, 292782] Funding Source: Academy of Finland (AKA)
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Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested sub-stance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.
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