Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Studying the Effects of the Intensity of US State Growth Management Approaches on Land Development Outcomes

Summary. Driven by negative externalities from suburban sprawl, many states in the US have adopted comprehensive growth management legislation in an effort to regulate land development more directly. Most extant scholarship evaluating the effects of growth management programmes employs a design that averages growth management’s effect across all of the growth management states. Yet, this approach largely ignores descriptive analyses of individual state growth management approaches which show large variation in both the methods and intensity of means by which states manage growth. This paper seeks to ascertain if differences in growth management intensity yield different evaluative outcomes. Analysis of panel data for nine growth management states using fixed effects regressions, across eight different model specifications, shows that only states with the strongest growth management intensity experience consistent success at reducing the expansion of urban land and increasing population densities. Beginning with the enactment of Hawaii’s Land Use Law in 1961, a number of US states have adopted comprehensive growth management legislation in an effort to pre

Structural Characterization of Campylobacter jejuni Lipooligosaccharide Outer Cores Associated with Guillain-Barré and Miller Fisher Syndromes

Molecular mimicry between lipooligosaccharides (LOS) of Campylobacter jejuni and gangliosides in peripheral nerves plays a crucial role in the pathogenesis of C. jejuni-related Guillain-Barré syndrome (GBS). We have analyzed the LOS outer core structures of 26 C. jejuni strains associated with GBS and its variant, Miller Fisher syndrome (MFS), by capillary electrophoresis coupled with electrospray ionization mass spectrometry. Sixteen out of 22 (73%) GBS-associated and all 4 (100%) MFS-associated strains expressed LOS with ganglioside mimics. GM1a was the most prevalent ganglioside mimic in GBS-associated strains (10/22, 45%), and in eight of these strains, GM1a was found in combination with GD1a mimics. All seven strains isolated from patients with ophthalmoplegia (GBS or MFS) expressed disialylated (GD3 or GD1c) mimics. Three out of 22 GBS-associated strains (14%) did not express sialylated ganglioside mimics because their LOS locus lacked the genes necessary for sialylation. Three other strains (14%) did not express ganglioside mimics because of frameshift mutations in either the cstII sialyltransferase gene or the cgtB galactosyltransferase gene. It is not possible to determine if these mutations were already present during C. jejuni infection. This is the first report in which mass spectrometry combined with DNA sequence data were used to infer the LOS outer core structures of a large number of neuropathy-associated C. jejuni strains. We conclude that molecular mimicry between gangliosides and C. jejuni LOS is the presumable pathogenic mechanism in most cases of C. jejuni-related GBS. However, our findings suggest that in some cases, other mechanisms may play a role. Further examination of the disease etiology in these patients is mandatory

Measuring Tsunami Planning Capacity on U.S. Pacific Coast

Abstract: The U.S. Pacific coastal states are at risk from both locally and distantly generated tsunamis. This vulnerability can be reduced by effective hazard management plans, but no studies have been conducted to determine how local jurisdictions have incorporated tsunami hazard management into their planning frameworks. This paper analyzes the quality of hazard management plans from 43 coastal counties in these states. Plan quality was measured by a plan evaluation protocol defined by five components and 37 indicators. The results show that few Pacific coastal counties have prepared well for tsunamis. Most plans have a weak factual basis, unclear goals and objectives, weak policies, and few coordination and implementation mechanisms. The average plan quality score is 12.25 out of 50 points and 10 counties never mention tsunami risks in their local plans at all. This evaluation suggests that these jurisdictions need to build a solid factual basis about tsunami hazards, set appropriate goals and practical objectives, expand the array of tools used by planners, enhance interdisciplinary and interorganizational coordination mechanisms, and improve their mechanisms for plan implementation