Third, though multiple nominally significant relationships between genetic risk for individual psychiatric disorders and involvement with specific substances emerged, few survived correction for the large number of statistical tests performed. These results thus may represent spurious associations and should be interpreted with caution. However, given the consistency of certain associations (e.g., ADHD and nicotine use) with prior genetic (e.g., Chang et al., 2012) and epidemiological (e.g., Elkins et al., 2007; Lee et al., 2011) literature, they should not be dismissed outright. Notably, the only disorders with significant post-correction associations—MDD and SCZ—were those with the largest numbers of cases in the PGC cross-disorder meta-analysis (NMDD = 9227, NSCZ = 9379). Nominal associations may thus strengthen with larger discovery samples, which may provide more precise PRS estimates, as well as larger target samples. In support of this interpretation, repetition of schizophrenia PRS analyses with scores derived from the much larger second-generation PGC GWAS (NSCZ2 = 36,989) yielded associations that were generally stronger than those from the first-generation analyses (Supplementary Tables S6 and S7; see Supplementary Figure S3 for comparison).
