Gene-based tests of association with initiation and age at onset were carried out by using the gene-based association test that employs the extended Simes procedure (GATES) implemented in the Knowledge Based Mining System for Genome-wide Genetic Studies software (Li et al. 2011). Specifically, the Simes test extension was employed to combine the P-values of SNPs belonging to the same gene. SNPs were assigned to genes (or to genes’ vicinity, i.e., within a region extended 5 kb at both the 5′ and at the 3′ ends) according to the Human Genome version 19 references. The LD structure was derived based on the GoNL haplotypes and incorporated into the gene-based test as to account for the correlatedness among SNPs within a gene. Lacking prior significant genetic association information related to the cannabis use phenotypes, SNPs were assigned equal weights in the estimation process and the gene-based tests were conducted genomewide for both phenotypes. There were 22 764 genes tested for association with our phenotypes, hence for the gene-based tests the chosen alpha level equaled 0.01/22 746 (i.e., ~4.3 × 10−7).
