There is also a growing recognition that endophenotypes may not be genetically simpler than the psychiatric phenotypes with which they are associated [118], and in fact may reflect the contribution of many genetic variants of small effect from across the genome [119]. A recent special section in the journal Psychophysiology (December 2014) devoted to studies of physiological candidate endophenotypes for addiction and schizophrenia in the Minnesota Twin and Family Study reiterates this point. These studies were able to use the same sample of parent and twin pair offspring to conduct biometric modeling (i.e., decomposing variation for a measure into latent genetic and environmental influences based on the pattern of correlations among different degrees of relatives) and genetic association analyses. In one example, biometric modeling indicated that genetic factors accounted for 65% of the variance in P3 amplitude; however, a genome-wide association study in the same sample did not identify any genome-wide significant variants, although a gene-based test did identify the myelin expression factor 2 (MYEF2) gene on chromosome 15 [120]. The absence of genome-wide significant effects suggests that P3 amplitude is likely polygenic. We return to the implications of a polygenic architecture for endophenotypes shortly.
