This special review issue on Neurological and Psychiatric Diseases and Traits focuses upon a number of phenotypes which, while very diVerent, result from impairment of, or variation in, some aspect of brain function. The brain is widely regarded as one of the most challenging subjects for biomedical research. Its anatomical organization is highly complex, its functional organization is poorly understood, and notwithstanding advances in neuroimaging, it remains relatively inaccessible to direct study in vivo. Moreover, whereas the wider functions of most organs can be understood in basic biochemical and/or physical terms, this is not often the case for the brain. For example, the genesis of the higher order brain functions that are often central to brain disorders such as self-awareness, perception, thought, mood, and volition cannot be readily understood in terms of fundamental molecular mechanisms. In many cases, to these diYculties can be added a deWciency of relevant molecular and phenotypic model systems, the beneWts of which are illustrated herein by the review of Down syndrome (Patterson 2009). While brain disorders are undeniably challenging targets for biomedical research, they are also amongst the most important, the brain being central to every aspect of human life. With its role in human adaptability and survival, it would be remarkable if traits that result from variation in brain function were not inXuenced in part by genes. However, even in fairly recent times, the hypothesis that genes contribute to variation in normal cognitive and behavioural traits has been controversial. As illustrated by the articles on human intelligence (Deary et al. 2009) and on aggression (Craig and Halton 2009), there is now convincing evidence (some of it old) that genes are involved, and the same is true for many other cognitive and behavioural traits. Genetic methods, therefore, oVer one possible route to trying to understand normal variation in brain function. The other reviews have as their subjects heritable brain-related phenotypes that are generally thought of as ‘disorders’; like intelligence and aggression, some of these can alternatively be conceptualized as quantitative traits, as illustrated in the review of ADHD by Franke and colleagues. In addition to the general diYculties alluded to above, many of the disorders reviewed herein also have features that make genetic studies problematic. Discussed in detail in the review of psychosis (O’Donovan et al. 2009), often the disorders cannot be classiWed based upon any biologically validated methodology. Consequently, the power of genetic studies is likely to be compromised by sub-optimal phenotypic deWnitions and extensive heterogeneity. In some cases, it has been possible to overcome this by identifying relatively homogenous groups based upon the presence of other syndromic features and/or by studying large single families co-segregating major genes, as exempliWed in the reviews of epilepsy (Andrade 2009) and migraine (de Vries et al. 2009). However, such approaches are not currently applicable to the majority of people with those disorders, or to individuals with other common neurological and psychiatric phenotypes. Another approach that has met with considerable success in identifying genes that contribute to Mental Retardation has been the study of balanced translocations (Vandeweyer and Kooy 2009) and other chromosomal abnormalities. Such gross abnormalities may not contribute substantially to typical forms of common disorders. However, studies of smaller chromosomal abnormalities in the form of rare copy number variants are beginning M. C. O’Donovan (&) · M. J. Owen Department of Psychological Medicine and Neurology, School of Medicine, MRC Centre for Neuropsychiatric Genetics and Genomics, Heath Park, CardiV CF23 6BQ, UK e-mail: odonovanmc@cf.ac.uk