The analyses conducted in this study involved testing whether the genetic variants underlying alcohol problems in one sample type (e.g. population-based or ascertained) were associated with alcohol problems to the same degree in independent samples from the same versus different sample types. We used polygenic risk score methods to take information about which genetic variants, or single nucleotide polymorphisms (SNPs), were associated with alcohol problems in one sample and applied this to create individual-level genetic risk scores (aggregated across genomic loci) in each of the other samples. Our analytic plan thus included two steps: first, obtaining SNP weights from a GWAS of alcohol problems in each “discovery” sample, and second, creating polygenic scores and testing how well they predicted alcohol problem risk in each independent “validation” sample. As an additional attempt to improve discovery power, we also conducted a meta-analysis of the individual GWAS within each sample type (ALSPAC+FT12 and COGA+IASPSAD) and used these meta-analysis summary statistics to create additional polygenic scores in the two samples of the other type. Each of the four study samples was therefore used once
