GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia

Source:

Pasman, J. A., Verweij, K., Gerring, Z., Stringer, S., Sanchez-Roige, S., Treur, J. L., Abdellaoui, A., Nivard, M. G., Baselmans, B., Ong, J. S., Ip, H. F., van der Zee, M. D., Bartels, M., Day, F. R., Fontanillas, P., Elson, S. L., 23andMe Research Team, de Wit, H., Davis, L. K., MacKillop, J., … Vink, J. M. (2018). GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia. Nature neuroscience, 21(9), 1161–1170. https://doi.org/10.1038/s41593-018-0206-1

Abstract

Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study for lifetime cannabis use to date (N=184,765), we identified 8 genome-wide significant independent single nucleotide polymorphisms in 6 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 non-users. 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 substance use and mental health 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 gives new insights about the etiology of cannabis use and its relation with mental health.