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

Analyse multicritère du potentiel d’utilisation d’écosystèmes côtiers pour la gestion des désastres naturels en Inde

Au cours des dernières décennies, les aléas hydrométéorologiques ont apporté un nombre grandissant de désastres naturels à l'échelle planétaire et sont associés à des pertes économiques de plusieurs milliards de dollars américains chaque année. Parmi les régions vulnérables, les zones côtières subissent généralement des impacts plus sévères. La contribution exacte des changements climatiques à la fréquence et l'intensité de ces aléas demeure incertaine, mais la probabilité d'évènements météorologiques extrêmes est significativement accrue avec l'augmentation de la température moyenne planétaire. Les autorités responsables doivent donc élaborer des plans d'adaptation et de gestion des risques afin de réduire les impacts, protéger leur population et maintenir leur économie. Une des voies envisagées est l'utilisation des écosystèmes pour la prévention, protection et mitigation des impacts des aléas dans les zones côtières. La dégradation soutenue des écosystèmes côtiers a mené à des impacts négatifs sur la résilience des populations locales, il est donc plausible que la conservation, la valorisation ou la restauration de ces écosystèmes puissent avoir un impact inverse. L'objectif principal de cet essai est l'évaluation du potentiel d'utilisation des écosystèmes côtiers dans un plan de gestion des risques de désastres naturels des états indiens du Tamil Nadu, d'Andhra Pradesh et d'Odisha qui bordent le golfe du Bengale. Le niveau de risque de cette région est particulièrement élevé en raison de plusieurs facteurs incluant : le climat régional, la géomorphologie de la côte et le taux de pauvreté. L'identification des impacts potentiels des changements climatiques ainsi qu'une description approfondie des caractéristiques physiques et socioéconomiques du lieu d'étude ont permis l'identification et l'analyse subséquente de six mesures de gestion à l'aide de la méthodologie MCA4climate développée par le Programme des Nations unies pour l'environnement. Cette analyse a révélé que les mesures de gestion écologiques concordent avec tous les principes du développement durable et se démarquent avantageusement de leurs contreparties structurelles. Les résultats obtenus ont permis l'élaboration d'une série de cinq recommandations : 1) l'implémentation immédiate de mesures de gestion écologiques vu les délais requis pour leur pleine fonctionnalité, 2) l'intensification de la recherche sur les services et produits écologiques afin de mieux informer les autorités responsables, 3) la combinaison de différents types de mesures de gestion pour créer une synergie positive pour augmenter la performance, 4) la restriction de l'utilisation de mesures de gestion structurelles en raison de leurs lacunes sur le plan du développement durable et, finalement, 5) le renforcement de la Politique nationale sur la gestion des désastres naturels du gouvernement fédéral indien pour encadrer, suivre et supporter les efforts des autorités responsables des régions à risque élevé

Analysis of Shared Heritability in Common Disorders of the Brain

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology