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

Servicio social realizado en empresas públicas de Medellín departamento habilitación viviendas y corregimientos y veredas Factibilidad y diseño conceptual de un acueducto veredal en el corregimiento de Santa Elena

181 páginasRESUMEN: Como proyecto de grado se presenta a continuación el estudio del Acueducto de la Vereda San Ignacio, ubicada en el corregimiento de Santa Elena, y corresponde a los municipios de Rionegro y Guarne. Para el estudio mencionado, nos basarnos en informes ya realizados en otras veredas de los diferentes corregimientos de los municipios del Valle de Aburrá, además utilizamos un levantamiento topográfico hecho un año atrás, así como para un mejor conocimiento de las características de la zona (Accesos, corrientes de agua, usos del suelo, etc.), fue necesario el uso de la Plancha 147-111-13-2 y visitas periódicas al sitio de interés. En la vereda San Ignacio, existen algunas obras construidas anteriormente, pero ninguna con el debido diseño y consideraciones, es decir, los habitantes de la zona decidieron realizarlas sin asesoramiento profesional. Además, al estudiar y visitar las diferentes corrientes de agua cerca a la vereda, se concluye que el agua que estas están en capacidad de aportar al acueducto, son insuficientes para la demanda esperada, por lo cual queda para posterior estudio una nueva fuente que sea capaz de cubrir la necesidad. A pesar de su ubicación, la vereda San Ignacio, así como las demás veredas de este sector de Santa Elena, tienen el grave problema de la escasez de agua, como corriente importante existe la quebrada que lleva el mismo nombre del corregimiento, pero por limitaciones ambientales no es posible tomar demasiada agua de dicha fuente. Cabe anotar que en verano la región sufre de disminución considerable en el nivel normal de sus diferentes cauces. Luego, es un deber de los municipios correspondientes, así como de los habitantes del corregimiento, controlar el crecimiento desmedido de la población en los años futuros.ABSTRACT: As a graduation project, we present the foliowing research about San lgnacio's path aqueduct in Santa Elena Village, and it corresponds to the municipalities of Rionegro and Guarne. For this research, we based Qn reports already done in others paths of the different villages of the Aburra Valley municipalities; besides, we made use of a topographical study done one year ago. As soon as to a much better comprehension of the area (accesses, runnings, earth uses, etc), it was necessary the use of the 147-111-13-2 lithographic printing plate and periodical inspection 5. In San Ignacio Path, there exist sorne constructions built before, but each one of them without the right design, that's to say, the inhabitants of the area made them without any professional counsel. Furthermore, studying and visiting the different runnings near to the path, one conclude that the water they bear to the aqueduct is not enough, having mio account the expected demand. For this reason, we expect a new research on a source of a river that cover up the demand. In spite of its location, San Ignacio Path, as soon as the others paths of 'che Santa Elena area, has the serious problem of lacking water. There exists an importani source of water, a brook that bears the same name of the village (Santa Elena) but due to environmental iirnitations it is not possible to take much water from that source of a river. In summer the different sources of the rivers diminish amazingly. So, the competent public institutions and the inhabitants of the area must care about birth control in corning yearsPregradoIngeniero(a) Civi

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