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Chunk #16 — Methods — Statistical analysis

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A large-scale genome-wide association study meta-analysis of cannabis use disorder.
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The FUMA web-based platform25 version 1.3.5e was used for visualisation and annotation, and MAGMA26 was used within the FUMA framework to do gene-based association analyses, with SNPs assigned to genes on the basis of physical position (appendix pp 14–15). We also used Hi-C coupled MAGMA to assign non-coding SNPs (intergenic and intronic) to genes on the basis of their chromatin interactions (exonic and promoter SNPs are still assigned to genes on the basis of their genomic location; appendix p 15).27 Pathway analyses were done using PASCAL to test canonical pathways in the European ancestry sample.28 All variants within all genes were tested, using default settings, with the structure of linkage disequilibrium estimated using the 1000 Genomes European sample as a reference. We used S-PrediXcan29 to examine gene expression differences associated with case-control status, using our summary statistics of cannabis use disorder and transcriptome data from the PredictDB Data Repository for 11 brain regions, liver tissue, whole blood, and two types of adipose tissue. We included these tissues because cannabis use disorder is a psychiatric disorder and tetrahydrocannabinol, a key psychoactive