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

Relações entre profissionais de saúde e usuários durante as práticas em saúde Relationships between health professionals and users throughout health care practices

Apresenta-se uma revisão integrativa sobre estudos que abordam as relações entre profissionais de saúde e usuários durante as práticas em saúde. Objetivou-se identificar os aspectos pesquisados no cotidiano dos serviços acerca dessas relações. A coleta foi realizada nas bases Lilacs e Pubmed segundo os descritores: acolhimento; relações profissional-família; relações profissional-paciente; humanização da assistência; e a palavra 'vínculo' associada ao descritor Sistema Único de Saúde. Selecionaram-se 290 estudos publicados entre 1990 e 2010. Por meio da análise temática, foram criados cinco núcleos de sentido: a relevância da confiança na relação profissional-usuário; sentimentos e sentidos na prática do cuidado; a importância da comunicação nos serviços de saúde; modo de organização das práticas em saúde; e (des)colonialismo. Identificou-se que as relações estabelecidas nas práticas de saúde têm uma dimensão transformadora. No entanto, permanece o desafio de humanizar os serviços de saúde. A enfermagem se destaca na produção do conhecimento nessa temática.<br>This article presents an integrative review about studies that address the relationships between health professionals and users in health care practices. It aimed to identify aspects that were researched on the daily life of the services concerning such relationships. Data were collected from the Lilacs and Pubmed databases based on these descriptors: user embracement; professionalfamily relations; professionalpatient relations; humanization of the care; and the bonding word associated to the Single Health System descriptor. Two hundred and ninety studies, published from 1990 to 2010, were selected. Through thematic analyses, five meaning cores were created: the relevance of the confidence in the professionaluser relationship; feelings and senses in the health care practice; the importance of communications in health care services; ways to organize health care practices and (de)colonialism. It was found that relationships established in health care practices have a transformative dimension. However, the challenge to humanize health care services remains. Nursing stands out in the production of knowledge on such theme

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