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Chunk #21 — Results — SNP-based heritability and genetic overlap with lifetime cigarette smoking

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Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.
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Using the density estimation method (see ‘Materials and Methods' section for a description), all the SNPs available in at least 25% of the samples when combined explained 20% of the total variance in lifetime cannabis use (P<0.001). Alternative estimation with LD score regression also yielded a significant heritable component of 13% (h2LD=0.13, s.e.=0.02, P=1.4 × 10−7). These variance estimates were robust across pruned sets with similar r2 thresholds (see Supplementary Table 6). Stricter LD pruning (that is, r2=0.05), or restricting analyses to SNPs present in all studies substantially decreased the estimate of variance explained. Both SNP heritability estimates confirmed that lifetime cannabis use has a significant heritable component (13–20%), indicating that GWAS should be able to identify these common SNPs (but effect sizes are small and large sample sizes are thus required). However, because these estimates are only based on common SNPs, the total heritability of lifetime cannabis use is likely to be higher.