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

Teores naturais de bário em solos de referência do estado de Pernambuco

O bário (Ba) é um metal alcalino terroso de ocorrência natural no solo. É constituinte de carbonatos, sulfatos e silicatos e ocorre como substituto isomórfico de elementos como Ca e K nos minerais. Quando disponível em elevados teores no solo, o Ba pode causar toxidez a diversos organismos vivos. Para considerar que determinado solo está livre de contaminação por esse elemento, faz-se necessário conhecer os teores de Ba nesse solo em condição natural. Portanto, a determinação de teores naturais de Ba em solos é essencial para a construção de uma legislação que sirva de base ao monitoramento e remediação de áreas contaminadas por esse elemento e que seja adequada à realidade pedológica local. Nesse contexto, o objetivo desta pesquisa foi determinar os teores naturais de Ba como base de referência de qualidade para os Solos de Referência do Estado de Pernambuco. Foram coletadas amostras dos dois primeiros horizontes dos 35 perfis de referência, as quais foram submetidas à digestão ácida em micro-ondas (método 3051A). Nos extratos obtidos foi efetuada a determinação dos teores de Ba por ICP-OES. Observaram-se teores de Ba superiores aos valores de prevenção e de investigação estabelecidos pela legislação brasileira (CONAMA, 2009), corroborando a necessidade de maior conhecimento das diversidades regionais para a elaboração de normas nacionais. Os teores naturais de Ba determinados nos solos podem ser utilizados como base para a definição dos valores de referência de qualidade para Ba nos solos de Pernambuco, de acordo com o preconizado pela legislação nacional