Knowns and unknowns for psychophysiological endophenotypes: integration and response to commentaries.

We review and summarize seven molecular genetic studies of 17 psychophysiological endophenotypes that comprise this special issue of Psychophysiology, address criticisms raised in accompanying Perspective and Commentary pieces, and offer suggestions for future research. Endophenotypes are polygenic, and possibly influenced by rare genetic variants. Because they are not simpler genetically than clinical phenotypes, they are unlikely to assist gene discovery for psychiatric disorder. Once genetic variants for clinical phenotypes are identified, associated endophenotypes are likely to provide valuable insights into the psychological and neural mechanisms important to disorder pathology. This special issue provides a foundation for informed future steps in endophenotype genetics, including the formation of large sample consortia capable of fleshing out the many genetic variants contributing to individual differences in psychophysiological measures.