Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction

Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.5 million people, our approach is statistically more powerful than single-trait analyses and identifies more than 500 genetic loci. The loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results predicts a range of behavioral and medical outcomes that were not part of genome-wide analyses, including traits that until now lacked well-performing polygenic scores, such as opioid use disorder, suicide, HIV infections, criminal convictions and unemployment. Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental trait with complex and far-reaching social and health correlates

Loss of Biological Diversity: A Global Crisis Requiring International Solutions: A Report to the National Science Board

Executive Summary Biological diversity refers to the variety and variability among living organisms and the ecological complexes in which they occur. Diversity can be defined as the number of different items and their relative frequency. For biological diversity, these items are organized at many levels, ranging from complete ecosystems to the chemical structures that are the molecular basis of heredity. Thus, the term encompasses different ecosystems, species, genes, and their relative abundance (OTA, 1987). There is an ongoing, unprecedented loss of the variety as well as absolute numbers of organisms-from the smallest microorganism to the largest and most spectacular of mammals. Loss of tropical moist forests, which contain over half the total species of organisms, has been well documented by scientists and is now widely reported in the media. Many other ecosystems are also threatened; as human populations and their support systems expand, natural ecosystems at all latitudes are altered or converted. At its meeting on October 15, 1987, the National Science Board concluded that the world\u27s decreasing biological diversity is a critical scientific issue requiring immediate attention. The National Science Board\u27s Committee on International Science was asked to study the scientific and international aspects of the decline of biological diversity and to recommend a course of action. This report describes what the National Science Foundation (NSF) can do to influence the U.S. science and education base, articulates where international scientific cooperation is needed, and suggests roles for other agencies and organizations (both national and international) which have scientific, educational, and management responsibilities. The current disappearance of biota has several causes: the destruction or degradation of entire ecosystems; the accelerating loss of individual species from communities or ecosystems as a result of human disturb;mce; and the loss of genetically distinct parts of populations due to human-induced selective pressures. Although not all parts of the planet are equally affected, the problem is global, and human activities are the primary cause. The loss of biological diversity is important because human existence depends on the biological resources of 1 the earth. Human prosperity is based very largely on the ability to utilize biological diversity: to take advantage of the properties of plants, animals, fungi, and microorganisms for food, clothing, medicine, and shelter. Scientific knowledge about the earth\u27s biological diversity has huge gaps. This lack of information hampers society\u27s ability either to estimate the magnitude of the problem or to prevent further losses. It is impossible to identify all the biological resources at risk, since there is no complete inventory of all the life forms on earth. Approximately 1.4 million species have been given scientific names, but estimates of actual numbers range from 5 million to 80 million species. Although knowledge of some taxa is extensive, the vast majority of groups are largely unknown. The current wave of extinction is destroying both known biotic resources and those still undiscovered. As is proving to be the case with most environmental problems, neither the loss of biological diversity nor its solution is the exclusive province of any one nation. International cooperation is necessary to develop both scientific knowledge and successful mitigation and management strategies. The root causes of the problem include sociological and economic processes which operate on an global scale; a thorough understanding will require investigation and elucidation of both biological and non-biological components. There are several reasons for increasing National Science Foundation (NSF) involvement in biodiversity studies: the economic and social importance of biodiversity (and the risk of opportunity lost due to accelerating extinction); the contributions such leadership can make toward to conservation of biological diversity; the important role of such studies in the international growth of science, especially in tropical countries; the potential impact of such studies on the future course of biology as a whole; and enhancing public awareness of the issues. NSF should assume a scientific leadership position with respect to agencies in the U.S. and throughout the world. By insisting on the central importance of biodiversity, the NSF could encourage collaborative support for the actions recommended below. 1. The Committee believes that the role of the NSF is clear-NSF should, as a matter of National Science Board Policy, provide leadership to undertake the inventory of the world\u27s biodiversity. 2. The scientific basis for conservation biology, restoration ecology, and environmental management must be strengthened. 3. Educational and public awareness programs related to biodiversity need increased support. 4. The economic and social aspects of the biodiversity crisis need additional study. 5. Enhance support for developing country scientists and institutions for biodiversity research and conservation

The Firre locus produces a trans -acting RNA molecule that functions in hematopoiesis

Abstract: RNA has been classically known to play central roles in biology, including maintaining telomeres, protein synthesis, and in sex chromosome compensation. While thousands of long noncoding RNAs (lncRNAs) have been identified, attributing RNA-based roles to lncRNA loci requires assessing whether phenotype(s) could be due to DNA regulatory elements, transcription, or the lncRNA. Here, we use the conserved X chromosome lncRNA locus Firre, as a model to discriminate between DNA- and RNA-mediated effects in vivo. We demonstrate that (i) Firre mutant mice have cell-specific hematopoietic phenotypes, and (ii) upon exposure to lipopolysaccharide, mice overexpressing Firre exhibit increased levels of pro-inflammatory cytokines and impaired survival. (iii) Deletion of Firre does not result in changes in local gene expression, but rather in changes on autosomes that can be rescued by expression of transgenic Firre RNA. Together, our results provide genetic evidence that the Firre locus produces a trans-acting lncRNA that has physiological roles in hematopoiesis

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects

Promoting School Earthquake Safety through a Classroom Education Grassroots Approach

The earthquake engineering community has recognized that in seismically active regions throughout the United States, hundreds of thousands of students and staff unknowingly study and work in structurally vulnerable school and university buildings. The School Earthquake Safety Initiative (SESI), spearheaded by the Earthquake Engineering Research Institute (EERI), is a collaborative network of diverse, expert, and impassioned professionals who are committed to creating and sharing knowledge and tools that enable broadminded, informed decision making around school earthquake safety. The Classroom Education and Outreach Subcommittee of SESI is tackling the problem of school safety from a grassroots approach, with the goal of using education in the classroom to create on ongoing dialog with parents, teachers, and administrators thereby developing advocates for earthquake school safety. To do so, well-defined K-12 engineering curriculum aligned with standards that are well documented and can be easily taught to a range of teachers for broad dissemination have been developed for 4th grade and high school physics classes. The modules lead students through hands-on and research activities to learn basic earthquake engineering design principles and make use of an electronic instructional shaking table that allows students to test structures under representative earthquake loading. In an effort to reach a large number of schools across the country, the initiative is engaging regional professional and university student chapters to work closely with classroom teachers and collaborate on delivering the activities