Our study should be interpreted in the context of several limitations. First, our sample size was relatively small. Second, because the COGA case–control alcohol dependence sample is highly affected by AAB, the findings emerging from our study may not generalize to lower-risk populations or other types of high-risk populations. Our null replication attempt may be attributable, in part, to the replication sample being relatively less affected than the discovery sample. There are other instances where genetic associations for externalizing behaviors have replicated within highly affected samples, but not less-affected samples. For example, GABRA2 is associated with alcohol dependence in samples where alcohol-dependent cases came from clinically recruited samples and families densely affected by alcoholism,54, 55, 56 but not community-based samples.57 A sample recruited for this purpose is likely to be enriched for genetic variation that predisposes individuals to a range of externalizing behavior problems, including AAB;18 however, whether our findings generalize to other populations at high risk for AAB (for example, incarcerated inmates58) is unknown. Third, because we limited the current analyses to European-Americans, our results may not generalize to other racial and ethnic groups.
