The limited overlap in linkage findings when the temporal clustering of symptoms was and was not required for the alcohol dependence diagnosis was somewhat unexpected, and merits further investigation. In a previous study, we estimated the average age-of-onset of the 36 ‘alcohol related life events’ assessed by the SSAGA, including the 12 alcohol dependence symptoms described in the present study, in the UCSF Family Study (Ehlers et al., 2010). Applying those data to the present study, we observed that linkage evidence for the alcohol dependence diagnosis when the temporal clustering of symptoms was required was driven by symptoms with a later age-of-onset that were more characteristic of the long-term consequences of persistent drinking, whereas linkage evidence for the alcohol dependence diagnosis when the temporal clustering of symptoms was not required was driven by symptoms with an earlier age-of-onset that were more characteristic of the short-term consequences of drinking. This provides a demonstration of how differences in ascertainment or phenotyping strategies can result in biases toward specific genetic liabilities involved in alcohol misuse and away from others.
