One presumed advantage of neurobiologically informed endophenotypes is that their associated genetic effect sizes should be larger than they are for their more complex and distal but related clinical phenotypes. We had 80% power to detect effects accounting for 1.4% of the variance in P3 amplitude, as one example. When we began this molecular-genetic project in 2007, we were thus optimistic that our large sample would prove adequate for the purpose. Our results indicate that a much larger sample would be needed. While it would of course be desirable to substantially increase sample size, it is important to consider how large would be large enough given the cost, time, and effort to collect this type of laboratory data. For P3 amplitude, which has strong support as an endophenotype for substance use and related child and adult externalizing disorders (which, as noted above, are well represented in the MTFS), our largest effect accounted for .33% of the variance. We would need 20,000 individuals to have sufficient power to detect an effect of this magnitude. Even with such a large sample, that
