To appreciate achievements in psychiatric genetics and to confront emerging challenges, we must, at the outset, examine whether studies aimed at identifying disease-related genetic variation are worthwhile. In particular, critics have argued that risk-attributable effect sizes are too modest, at least for common variants (e.g., OR < 1.1), to be therapeutically meaningful. From a public health perspective, only a few might argue that highly heritable traits, such as Autism Spectrum Disorders, Schizophrenia, Bipolar Disorder and Late-Onset Alzheimer’s Disease should not be interrogated using genetic approaches. However, some may propose that the pursuit of common variant association identification has either not yielded sufficiently new discoveries or, as for Schizophrenia, has reached an asymptote where the clinical relevance of every new discovery may not be as proportionally related to magnitudes of sample size, effort and continued funding, particularly as newly discovered variants are likely to be associated with increasingly smaller effect sizes. Similarly, there has been skepticism regarding investment of resources to gene discovery for disorders such as depression and addictions (Merikangas and Risch, 2003), that are less heritable. The skeptical argument
