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Chunk #46 — Methods — Statistical analyses — Replication

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Genome-wide association study implicates CHRNA2 in cannabis use disorder.
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The genome-wide significant locus on chromosome 8 was replicated in an independent European cohort consisting of 5,501 cases with diagnosed CUD and 301,041 population controls collected by deCODE genetics. The characteristics of the SAA treatment sample have been described previously20 and currently diagnoses at Vogur Hospital are made using DSM-V, but most of the diagnoses in this study are based on DSM-IV or DSM-IIIR. The genotypes were obtained based on SNP array data and whole genome sequences using long range phasing and two types of imputations70. For the replication study, markers were looked up in the results of a GWAS performed by logistic regression treating disease status as the response and genotype counts as covariates. Other available individual characteristics that correlate with disease status were also included in the model as nuisance variables, using previously described methods71. The resulting P-values were corrected for inflation by the method of genomic controls (correction factor=1.42). Nine genetic variants all representing the same association signal on chromosome 8 with P-values less than 1x10−6 were looked up in the deCODE results. The variants in the