COMMENTARY The genetic architecture of psychophysiological phenotypes

It is now clear that almost all complex traits have a highly polygenic component; that is, their genetic basis consists of relatively frequent risk alleles at a very large number of loci, each making a small contribution to variation, or disease susceptibility. This general conclusion appears to hold for intermediate phenotypes. Therefore, we should not expect these phenotypes to be associated with substantially larger effect sizes than conventional phenotypes. Instead, their usefulness is likely to lie in understanding the mechanism underpinning associations identified via genome-wide association studies of conventional phenotypes. Descriptors: Genetics, Genetic architecture, Intermediate phenotypes, Genome-wide association study Psychological and behavioral traits are under a considerable degree of genetic influence, with typical heritability statistics in the 0.40– 0.60 range, but specific genetic variants associated with these traits have proved elusive. Since the first molecular genetic studies in the 1990s, there have been numerous reports of genetic association that have failed to consistently replicate. Early candidate gene studies selected variants for investigation on the basis of the know