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Chunk #16 — Materials and methods — Statistical analyses — Estimation of 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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The proportion of phenotypic variance that could be explained by the SNPs was estimated using the density estimation method developed by So et al.41 The density estimation method estimates the genome-wide distribution of effect sizes based on the difference between the observed distribution of test statistics in the meta-analysis and the corresponding null distribution. Before estimation, the SNPs present in at least 25% of the meta-analysis samples were pruned for LD. We used the r2=0.15 pruning level as the primary result for consistency with other applications of this method. Additional details are located in the Supplementary Information 2. LD Score regression42, 43 was used as an alternative method to estimate the SNP-based heritability, as well as to estimate the degree of genetic covariance between lifetime cannabis use (present study) and lifetime cigarette smoking31 (see Supplementary Information 2).