Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Social Influences and Behavior Outcomes: A Study to Determine an Adolescent Profile At-Risk for Substance Abuse

Abstract not availabl

Construire le voisin. Pratiques européennes

Lancée en 2003, la Politique européenne de voisinage est devenue l’axe majeur des relations extérieures de l’Union européenne. Jamais, en effet, une initiative de politique étrangère n’avait connu un tel engouement au niveau communautaire. Il faut dire que l’Union entend pour la première fois proposer à ses voisins une politique compréhensive, qui articule les interactions commerciales aux échanges sociaux et culturels. Les articles de ce numéro, à travers une analyse serrée des textes et des enquêtes de terrain, mettent en relief d’autres projets, d’autres dynamiques et d’autres conséquences. En effet, loin d’être une politique construite avec les voisins, la politique européenne de voisinage semble imposer aux voisins les cadres cognitifs et normatifs de l’Union. Celle-ci, sous couvert de vouloir aider ses voisins, n’est-elle pas en train de mettre en place une situation d’hégémonie ? Lorsqu’elle parle d’inclusion économique, l’Union européenne ne promeut-elle pas simultanément l’exclusion institutionnelle et politique des Etats voisins ? Et lorsqu’elle évoque la frontière, ne peut-on pas détecter en creux un projet identitaire aux contours incertains ? La construction du voisin qui semble ainsi s’opérer par cette politique européenne ressemble moins au partenariat d’égal à égal annoncé qu’à une forme de tutorat ambigu et inavoué… Launched in 2004, the European Neighbourhood Policy (ENP) has become one of the main dimensions of the external relations of the European Union. Never had a foreign policy initiative provoked such an enthusiasm at the community level. For the first time, the Union has indeed proposed a comprehensive policy to its neighbours, articulating commercial interactions on the one hand, social and cultural relations on the other. The articles in this issue, based on thorough analyses of the relevant texts as well as on field studies, unveil the other projects, dynamics and consequences underlying the European Neighbourhood Policy. Indeed, far from being defined with the neighbours, the European Neighbourhood Policy seems to impose the cognitive and normative frameworks of the Union upon the latter. Is this policy not furthering hegemony in the guise of good neighbourhood relations? When invoking economic inclusion, is the EU not fuelling the institutional and political exclusion of the neighbouring states? When dealing with borders, is it not a yet largely indeterminate form of identity politics that is being articulated? The construction of the neighbour underlying this European policy has in fact less in common with the equal partnership that is announced than with a form of ambiguous and implicit tutelage

The Impossible Self

Conceived of as a "sequel" to "Space Invaders", the exhibition investigates the relationship between art and popular culture. Work by nine international artists is brought together with two essays, extensive interviews and artist's statements to develop various concepts of the self in Western thought and cultural production