Neuroimaging endophenotypes: Strategies for finding genes influencing brain structure and function

Abstract: It is vitally important to identify the genetic determinants of complex brain-related disorders such as autism, dementia, mood disorders, and schizophrenia. However, the search for genes predis-posing individuals to these illnesses has been hampered by their genetic and phenotypic complexity and by reliance upon phenomenologically based qualitative diagnostic systems. Neuroimaging endo-phenotypes are quantitative indicators of brain structure or function that index genetic liability for an illness. These indices will significantly improve gene discovery and help us to understand the func-tional consequences of specific genes at the level of systems neuroscience. Here, we review the feasibil-ity of using neuroanatomic and neuropsychological measures as endophenotypes for brain-related dis-orders. Specifically, we examine specific indices of brain structure or function that are genetically influ-enced and associated with neurological and psychiatric illness. In addition, we review genetic approaches that capitalize on the use of quantitative traits, including those derived from brain images