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Chunk #10 — Discussion

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GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia.
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There are two previous studies that found significant SNP associations for a cannabis use phenotype. Sherva et al. (2016, 46) found 3 SNPs significantly associated with cannabis dependence. In our results only one of the SNPs was available (rs77378271) and was not significantly associated with lifetime cannabis use (p=.144). The other 2 SNPs (rs143244591 and rs146091982) or their high LD proxies were not available in our data. The SNPs rs77378271 and rs146091982 were located in genes CSDM1 and SLC35G1 respectively, and neither of those were significant in our gene-based results (p=0.96 and p=0.49, respectively). Demontis et al.11 found one independent significant signal at chromosome 8 to be associated with cannabis dependence (with top SNP rs56372821, a strong eQTL for CHRNA2). Neither the SNP (p=0.55) nor the gene (p=0.52) was significantly associated with lifetime cannabis use in our study. The protein encoded by CHRNA2 is a subunit of certain nicotinic acetylcholine receptors and Demontis et al.11 provide three potential biological explanations for the link between cannabis intake and CHRNA2. However, it is possible that while CHRNA2 is associated with cannabis dependence,