The allelic effects which we were able to detect are associated with relative risks of 1.1 to 1.2 for development of alcohol dependence, particularly dependence with onset of symptoms after the age of 25 (Table 5, Figure 2). This is consistent with recent estimates for detectable effects of other genes on risk of other diseases (Wellcome Trust Case Control Consortium., 2007). Detection of the expected large number of other polymorphisms producing small but collectively important effects on AD risk will require even larger individual studies, and meta-analysis across studies. In this connection it will also be important to test for heterogeneity across studies, and to seek explanations for any heterogeneity in areas such as study characteristics or populations studied. Given that GABRA2 variation has been shown to affect AD risk in multiple case-control studies based on clinical recruitment, it is notable that only small effects were found in our population-based cohort study. This emphasizes the need to evaluate allelic associations in diverse groups in order to form a full model of genetic effects on AD, and by implication for other complex diseases.
