The results of this study should be interpreted in the context of several important limitations. Foremost, the GWAS meta-analysis that was used to generate summary statistics within developmental periods was underpowered. Sample sizes were 8,869.29, 9,647.64, and 9,894.18 in adolescence, early adulthood, and adulthood, respectively. COGA was removed from the discovery analysis in Aim 2 to facilitate PGS construction, further reducing power. Second, estimates of H2SNP were small in each developmental period and the 95% confidence intervals for estimates derived from all stages of the analysis pipeline were large. As a result, point estimates should be interpreted cautiously. Third, these analyses only included European ancestry participants, limiting the generalizability these findings across ancestry groups. It is a critical priority to extend genetic analyses to a broader range of ancestry groups (Peterson et al, 2019). Fourth, we did not apply any transformations to our phenotypes, despite right-skew and zero-inflation in the distribution of adolescent alcohol use. This allows for intuitive interpretation of effect sizes in units of drinking days per year, but may have impacted results. Analysis with log transformed phenotypes
