We used a likelihood estimation-based approach to calculate the probability distribution of effect sizes for the addiction-rf and each of the constituent input GWASs (i.e., PAU, PTU, CUD, OUD) to examine relative differences in polygenicity (see Methods). The addiction-rf showed a narrow distribution of small effect sizes with almost all values falling close to 0. On the other hand, the original substance specific GWASs were characterized by larger average effects (see Supplemental Figure 6 for shape of probability density distribution). For example, only 26% of genes associated with Problematic Tobacco Use showed effect sizes as close to the mean threshold of the probability distribution as addiction-rf did. These findings suggest that the addiction-rf is characterized by greater polygenicity than specific substances.
