Association analysis based on Subsets (ASSET)24 was used to identify pleiotropic (i.e., SNPs that show associations with more than one SUD) and substance-specific (i.e., SNPs only associated with a single SUD) SNPs within the European and African American ancestry samples in addition to GenomicSEM in Europeans). ASSET was used in our African American ancestry addiction-rf GWAS as the sample size was not sufficient for the Genomic SEM approach used in the European addiction-rf GWAS. As a result, there are important differences in the primary addiction-rf GWAS and GWAS run in ASSET. First, the ASSET-based addiction-rf GWAS contain SNPs that may influence 2, 3, or all 4 individual SUDs, while the GenomicSEM-based addiction-rf GWAS in European ancestry includes SNPs associated with a common factor across included SUDs. ASSET identified pleiotropic SNPs in the European ancestry sample to facilitate method-consistent cross-ancestry meta-analysis GWAS (see subsequent Cross-Ancestry Meta-analysis section below) and cross validate primary GenomicSEM results.
