Not least is a very well-characterized psychiatrically normal control cohort. And, as with any new technology, there are considerable technical challenges, such as the use of whole-genome data to identify copy number variation. However, software is constantly developing and it is doubtful that these will be limiting factors for long.89 -92 There are also “genomic” challenges: Inhibitors,research,lifescience,medical there are many regions of the genome on which we tend not to focus, such as remote enhancer regions, upstream open reading frames, and chromatin binding sites, which are likely to be functional and affected by rare variation. However, using Mendelian diseases

as a model, it is reasonable to expect that many of the most important variants will be in or very close to exons.93 Thus, see more neuropsychiatric geneticists should be able to gorge themselves on the lowhanging fruit for some time to come. In summary, there have been many GWAS success stories Inhibitors,research,lifescience,medical in which common variants have been found to associate definitely with complex diseases. In most

cases, however, the mechanism underlying the association is not well understood, and they have not yet led to strong predictive tests or to novel treatments. Neuropsychiatric disease, Inhibitors,research,lifescience,medical in particular, has so far benefited little from large-scale analysis of common variants. Use of GWAS data to examine rare copy number variants, however, rapidly led to multiple strong and highly penetrant associations with neuropsychiatric illness. However, the associated variants are not completely penetrant and tend to be associated with multiple Inhibitors,research,lifescience,medical neuropsychiatric conditions. Detailed studies of patients and their relatives will be necessary to understand what factors affect the manifestation of the phenotype. Despite this recent success, we can still only account for a very small amount of the heritability of neuropsychiatric conditions. Further investigation of rare variation using whole-genome sequencing Inhibitors,research,lifescience,medical is likely to significantly advance the field.
The

introduction of personality disorders (PDs) as diagnostic categories on a separate axis (Axis II) in the third edition of the Casein kinase 1 Diagnostic and Statistical Manual of Mental Disorders (DSM-III) in 19801 had a dramatic effect on the level of interest in these disorders among researchers, and the number of published articles increased substantially. However, the number of genetic epidemiologic studies of the DSM PDs has remained limited compared with studies on both clinical disorders like schizophrenia, depression, and anxiety disorders (which are classified on Axis I in DSM), and on normal personality traits.2-4 The understanding of the role of genetic factors in the etiology of disorders and traits is inseparably linked to classification, since a precise definition of the phenotype is a prerequisite for all successful genetic studies.