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

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Can bryophytes be used to characterize hydrologic permanence in forested headwater streams?

Recent court cases have questioned whether all headwater streams, particularly those that are not perennial, fall within the protective boundaries of the Clean Water Act. Rapid field-based indicators of hydrologic permanence are critically needed for jurisdictional determinations. The study objective was to determine whether characteristics of bryophyte assemblages in forested headwater streams can be useful indicators of hydrologic permanence. We sampled bryophytes from the channel thalweg at 113 sites across 10 forests in the U.S. which varied in hydrologic permanence. Hydrologic permanence was based on hydrologic status during spring (wet season) and late summer (dry season) visits. Perennial sites had flow (surface or visibly interstitial) during both spring and summer visits. Intermittent sites flowed during spring but were either dry or had surface water limited to isolated pools in summer. Ephemeral sites did not have flow during either visit. The species composition significantly differed between ephemeral and perennial stream reaches. The species composition of intermittent streams overlapped with both ephemeral and perennial streams. Three species and six families were identified as indicators of particular permanence classes. Liverworts occurred more frequently at perennial than at intermittent or ephemeral sites. Bryophytes with cushion and turf growth forms were common to ephemeral sites, whereas mat and weft forms were more common to perennial sites. Acrocarpous mosses were more frequent at ephemeral than at perennial sites. The frequencies of bryophyte-moisture associations (derived from the literature) across the three permanence categories were significantly different. Species associated with dry habitats were more frequently encountered at ephemeral than perennial sites, whereas species associated with wet habitats were more frequent at perennial than ephemeral sites. Species richness varied among forests and permanence classes. Ephemeral sites tended to have higher species richness than perennial sites; however, this pattern did not hold for all forests. Bryophytes should be included among the tools for jurisdictional determinations, much like vascular plants are used to help delineate wetlands. Growth forms and higher level taxonomy of bryophytes (i.e., phyla) can be particularly useful for making jurisdictional determinations because of their ability to discriminate ephemeral from intermittent and perennial reaches and they are measures that can be rapidly trained and routinely used by agencies making such determinations

Extracting isovolumes from three-dimensional torso geometry using PROLOG

Three-dimensional (3-D) Imite element torso models are widely used to simulate deflbrillation field quantities, such as potential, gradient, and current density. These quantities are computed at spatial nodes that comprise the torso model. These spatial nodes typically number between 105 and 106, which makes the comprehension of torso deli brillat ion simulation output difficult. Therefore, the objective of this study is to rapidly prototype software to extract a subset of the geometric model of the torso for visualization in which the nodal information associated with the geometry of the model meets a specified threshold value (e.g., minimum gradient). The data extraction software is implemented in PROLOG, which is used to correlate the coordinate, structural, and nodal data of the torso model. A PROLOG-based environment has been developed and is used to rapidly design and test new methods for sorting, collecting, and optimizing data extractions from defibrillation simulations in a human torso model for subsequent visualization. © 1998 IEEE

Meningitis Due to a “Bartonella washoensis”-Like Human Pathogen▿

We report the second human case of infection caused by an organism identified as the proposed Bartonella species, “B. washoensis.” The organism was isolated from a blood sample from a patient presenting with meningitis and early sepsis. Oropsylla montana fleas were implicated as the vector for disease transmission in this case