These results, as tentative and in need of replication, if correct have implication for efforts to study genetic risk factors for AD. Prior twin or adoption studies have looked at the magnitude of aggregate genetic effects, developmental processes or patterns of comorbidity assuming that AD reflected a single dimension of genetic liability. These results will need to be reconsidered in light of evidence for multiple genetic factors underlying AD. Molecular genetic studies—particularly candidate gene and genome-wide association studies—have similarly focused almost exclusively on the comparison with subjects meeting the criteria for AD with matched controls. If correct, the results reviewed herein suggest that this approach would be at best inefficient. Cases and controls would likely differ on three relatively independent dimensions of genetic risk with the pattern and degree of difference varying considerably across individuals. As these results need replication before they should lead to widespread changes in analytic strategy, they highlight the assumption, widely accepted but rarely tested, that psychiatric and substance use disorders as described by current diagnostic systems reflect a single dimension of genetic risk. This assumption is unwarranted and should not continue to be accepted before being subjected to empirical test.
