Chunk #69 — Potential for Translational Applications of Electrophysiological Measures of Brain Function — Electrophysiological Measures As Endophenotypes for Alcoholism
Risk for alcoholism is complex and influenced by both genetic and environmental influences and their interactions: multiple genes, each with small effect, phenotypic complexity and heterogeneity, environmental variability, gene–gene interactions, and gene-by-environment interactions (Porjesz and Rangaswamy 2007). It is difficult to find genes affecting complex diseases such as alcoholism and to use diagnosis as the sole phenotype (Tsuang and Faraone 2000). One effective strategy to find genes is the “endophenotype” approach, first proposed by Gottesman and Shields (1972), who defined an endophenotype as an intermediary measure of neuropsychiatric functioning correlated with the main trait of interest and involved in the pathway between genotype and outcome of interest (Gottesman and Gould 2003). An effective endophenotype must meet three important criteria: (1) it is associated with the illness in the population (i.e., present in affected individuals); (2) it is heritable; and (3) it is found in unaffected relatives of probands at a higher rate than in the general population (including offspring before the onset of the illness). Neurophysiological quantitative measures that meet these three criteria can serve as effective endophenotypes. That is,
