The loss of genetic signal was evaluated using the five key indicators. First, down-sampling reduced the EffN of the two univariate GWASs on SMOK and CANN by about 47% and 12%, respectively (Table 1), which is a marked reduction with potential down-stream consequences. However, down-sampling did not meaningfully impact heritability estimates nor the attenuation/stratification bias ratio, which is important for expecting a comparable factor structure in the multivariate analysis below. Similarly, down-sampling did not meaningfully influence the genetic correlations among the seven indicator phenotypes (Fig. 1, Table S1), which increases the likelihood of obtaining a similar factor structure.