One potential explanatory concept is the existence of an endogenous neurophysiological endophenotype such as central nervous system disinhibition (Porjesz and Rangaswamy 2007). That is, if the mechanism underlying the association between GABRA2 and alcohol dependence is an endophenotype, individuals with the high-risk genotype might be susceptible both to alcohol dependence and to social conditions like divorce, unemployment, and social isolation that are associated with lower levels of positive daily experiences (i.e. a confounding effect). Based on prior research, the disinhibition phenotype is expected to be present to a greater degree in men than women (Cross et al. 2011), but we do note that the high-risk genotype is not associated with lower levels of daily uplifts among women or men without alcohol dependence in the COGA sample. That said, we cannot rule out the possibility that a neurophysiological endophenotype may have contributed to the etiological pathways that produce the observed patterns.
