Chunk #109 — 5. Implications for understanding gene-brain-behavior relationships in health and disease — 5.1. Intermediate phenotypes, or “endophenotypes”
How can the knowledge gained in genetic psychophysiology research help us to advance the broader field of behavior and psychiatric genetics? The first important contribution can be facilitation of gene finding. During the past two decades, enormous resources have been allocated to finding genes that confer liability to highly heritable psychiatric disorders and addictive behaviors such as schizophrenia, autism, ADHD, alcoholism, nicotine addiction, and other conditions. There was a great hope that the application of high-density arrays of genetic markers made available by the rapid progress in molecular genetics and the use of gigantic samples would lead to a quick progress in the identification of the genes responsible for these disorders. The results of early genome-wide association studies (GWAS) were largely disappointing because first positive findings were often refuted by subsequent studies based on even larger samples. For example, numerous large scale linkage and association studies of alcoholism have been conducted, but the agreement across studies was very poor and, by now, there is no single well-replicated finding of a gene conferring risk for alcoholism, except the genes encoding the
