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

Governing forward : thinking through law and governance to enable wider use of nature-based solutions in cities

Climate change and accelerating urbanization of human populations are increasing uncertainty and creating additional challenges to environmental and social well-being in cities. These changes require new and different approaches in development and governance of cities to achieve urban sustainability and urban resilience. This dissertation considers how governance in cities conditions the use of nature-based solutions (NbS) to address urban environmental challenges. I use empirical case studies of the experiences of two cities implementing nature-based solutions to understand the municipal governance regime around the use of nature-based solutions in each city and offer proposals to modify the relevant legal frameworks to better support use of the solutions. The first study uses a governance assessment tool previously applied by scholars in a variety of water governance and policy contexts to analyze the municipal governance regime for the implementation of NbS in Austin, Texas. The second paper applies an “emergence frontier” framework to explore how legal and institutional factors affect the emergence of adaptive governance and the implementation of NbS in Valladolid, Spain. The third paper explores the literature on adaptive law and the role of law in adaptive governance, and then uses the case studies developed in the first two papers as contexts for proposing specific changes to each city’s regulatory framework to facilitate the wide-spread use of nature-based solutions and to prompt decisionmakers to consider how regulatory frameworks, more generally, can be made more adaptable and better able to govern shifting social-ecological systems. In exploring the concept of adaptive law and considering how adaptive qualities and mechanisms in law and governance may be applied in municipal contexts to support the use of NbS in urban areas, I seek to contribute to filling a gap in scholarship concerning how law and governance arrangements can be shifted to facilitate the use of innovative solutions to integrate nature into cities and promote healthy urban social-ecological systems.Public Affair

Current challenges in the Rio Grande/Río Bravo Basin: old disputes in a new century

The Rio Grande River traverses 2000 kilometres of the international border between Mexico and the United States. The river and its tributaries are governed by a series of border treaties and institutions, as well as under the domestic laws of each nation. Often lauded for enabling innovative and collaborative governance, in recent years the complicated regime has come under pressure as domestic and international water governance institutions struggle under the strain of climate change, population growth, and other stressors on water supply and demand in the region. This chapter considers three of the major challenges currently facing the Rio Grande River Basin and its riparians: (1) groundwater and ground–surface interactions and related practical and policy implications; (2) engagement with local and regional stakeholders; and (3) Mexico\u27s latest water debt under the 1944 Treaty. It also identifies shortcomings in the regime to address these concerns, as well as innovative responses and solutions that have been crafted at various levels of governance

Minute 319: a cooperative approach to Mexico–US hydro-relations on the Colorado River

Minute 319 is the most recent amendment to the 1944 treaty governing the Colorado River, shared between Mexico and the United States. The amendment was adopted, in part, as a continuing response to the 2010 Mexicali earthquake, which severely damaged Mexican irrigation infrastructure, as well as ongoing objectives to address dwindling water supplies in the basin. By implementing measures to share both shortages and surpluses, and by facilitating long-term collaborative efforts that engender interdependencies, the amendment commits the parties to cooperate and may serve as a model for other regions sharing limited transboundary freshwater resources

Current challenges in the Rio Grande/Río Bravo Basin: old disputes in a new century

The Rio Grande River traverses 2000 kilometres of the international border between Mexico and the United States. The river and its tributaries are governed by a series of border treaties and institutions, as well as under the domestic laws of each nation. Often lauded for enabling innovative and collaborative governance, in recent years the complicated regime has come under pressure as domestic and international water governance institutions struggle under the strain of climate change, population growth, and other stressors on water supply and demand in the region. This chapter considers three of the major challenges currently facing the Rio Grande River Basin and its riparians: (1) groundwater and ground–surface interactions and related practical and policy implications; (2) engagement with local and regional stakeholders; and (3) Mexico\u27s latest water debt under the 1944 Treaty. It also identifies shortcomings in the regime to address these concerns, as well as innovative responses and solutions that have been crafted at various levels of governance

Emerging Legal Issues in Hurricane Damage Risk Abatement

The vulnerability of the U.S. coastline to severe storms is clear in the wake of Hurricanes Katrina, Sandy, Ike, and Wilma, which collectively amounted to over $200 billion in economic loss (NOAA 2013). The Houston-Galveston region alone experienced more than$25 billion in economic loss from Hurricane Ike in 2008, despite the fact that the greatest impact missed the region and instead hit east of Galveston Bay (Severe Storm Prediction, Education and Evacuation from Disaster Center 2015, 12). Since that time, the Severe Storm Prediction, Education and Evacuation from Disaster (SSPEED) Center at Rice University has been studying hurricane surge damage reduction strategies under a grant from the Houston Endowment. The goal of this work is to develop and evaluate structural and nonstructural alternatives to create a plan capable of significantly reducing hurricane surge damages in the Houston-Galveston region. Part of that research includes understanding the availability of federal funding to implement such a plan, as well as the policies that may apply to these federal funding opportunities. In turn, this research has revealed some very interesting and evolving policy trends regarding water projects and federal risk reduction. This paper explores some of the policy issues that arise in the context of the geographic and spatial challenges presented by Galveston Bay surge flooding. First, the extent of the problem is described. Second, various potentially applicable federal statutes, executive orders, and regulations are examined. Third, several proposed solutions for reducing surge flooding in the region are described and evaluated in the context of the policy initiatives from Congress and the executive branch. Finally, some conclusions are drawn and recommendations are offered for future research and implementation

Summary: Water and Energy Workshop—Understanding Impacts and Trade-Offs to Facilitate Transitions

This paper summarizes the presentations and discussions at May 14, 2015, workshop on water-energy interdependence and related issues. The Baker Institute Center for Energy Studies (CES) and the Texas A&M University Nexus Research Group convened the event

Summary of the 2014-15 Climate Lecture Series

This paper reports the key climate change and public policy issues addressed by guest speakers during the 2014-15 Climate Lecture Series hosted by the Center for Energy Studies

Confronting Climate Change: Policies and Opportunities

This report summarizes the perspectives of panelists at the conference “Confronting Climate Change: Policies and Opporturtunities,” held Oct. 22, 2015, at the Baker Institute. The Center for Energy Studies and the Consulate General of France in Houston hosted the event as part of FACTS (French Ameri-Can Climate TalkS), a series of public conferences in 12 cities across the United States and Canada involving academics, government officials, NGOs, political figures, journalists and entrepreneurs. The timing and subject matter were designed to contribute to civic dialogue as the world prepared for the United Nations Climate Change Conference in Paris in December 2015