Since AUD is a heterogeneous disorder, one approach has been to use intermediate phenotypes that reflect mediating factors in behaviors such as AUD, and are likely to be influenced by variation at fewer genes. The resting EEG is a dynamic index of cortical activation, cognitive function and consciousness and is therefore an intermediate phenotype for many behaviors in which arousal is implicated such as anxiety and AUD. A dense whole genome linkage scan in a large pedigree of Plains American Indians identified convergent genome-wide significant linkage peaks for EEG power on chromosome 5q13-14, at the apex of which was located CRHBP, a gene that encodes the binding protein for CRH, a key regulator of the stress response.48 CRHBP was significantly associated with EEG alpha power in the Plains American Indians and also in a replication sample of US Caucasians and was also associated with anxiety disorders in the Plains American Indians and AUD in the US Caucasians.48 Interestingly, the chromosome 5q13-14 CRHBP location was close to a linkage peak for alcohol craving in Southwest California Indians.49 The CRHBP gene has
