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

The genetics of the mood disorder spectrum:genome-wide association analyses of over 185,000 cases and 439,000 controls

Background Mood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders. Methods To clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424). Results Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell-types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder. Conclusions The mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development

A Camera-Trap Home-Range Analysis of the Indian Leopard (Panthera pardus fusca) in Jaipur, India

The suitability of the camera trap–retrap method was explored for identifying territories and studying the spatial distribution of leopards (Panthera pardus fusca) in the Jhalana Reserve Forest, Jaipur, India. Data from two years (November 2017 to November 2019, N = 23,208 trap-hours) were used to provide estimates of minimum home-range size and overlap. We conducted home-range analysis and estimation, using the minimum convex polygon (MCP) method with geographic information system (GIS) tools. We are aware of the limitations and advantages of camera trapping for long-term monitoring. However, the limitations of the research permit allowed only the use of camera traps to estimate the home ranges. A total of 25 leopards were identified (male = 8, female = 17). No territorial exclusivity was observed in either of the sexes. However, for seven females, we observed familial home-range overlaps wherein daughters established home ranges adjacent to or overlapping their natal areas. The median home range, as calculated from the MCP, was 305.9 ha for males and 170.3 ha for females. The median percentage overlap between males was 10.33%, while that between females was 3.97%. We concluded that camera trapping is an effective technique to map the territories of leopards, to document inter- and intraspecific behaviors, and to elucidate how familial relationships affect dispersal

Land Surface Temperature Regulation Ecosystem Service: A Case Study of Jaipur, India, and the Urban Island of Jhalana Reserve Forest

Although Land Surface Temperatures (LSTs) are on the rise globally, the distribution of LSTs varies depending on the land cover type. Urban Heat Island and Urban Cool Island effects act differently, especially in semi-arid regions. Therefore, we identify demi-decadal, seasonal, and zonal differences in LSTs in a semi-arid region in the city of Jaipur, where zones include rural and urban areas that encircle the Jhalana Reserve Forest (JRF). After deriving LSTs from remotely sensed thermal bands of Landsat satellites’ Multi-spectral datasets, we found that there is a significant difference in LST (p < 0.01) among the zones. In addition, LSTs were found to be significantly lower in JRF compared to Urban and Rural areas in all seasons and all study years, which indicates the urban cooling effect due to the presence of the forest. Nevertheless, summer LSTs have warmed with a mean difference of 4.8 °C between 2000 and 2020. Therefore, our study supports the promotion of Urban Forests, especially in semi-arid zones, for inculcating LST regulation ecosystem services to enrich and enhance the standard of living of the human population

Land Surface Temperature Regulation Ecosystem Service: A Case Study of Jaipur, India, and the Urban Island of Jhalana Reserve Forest

Although Land Surface Temperatures (LSTs) are on the rise globally, the distribution of LSTs varies depending on the land cover type. Urban Heat Island and Urban Cool Island effects act differently, especially in semi-arid regions. Therefore, we identify demi-decadal, seasonal, and zonal differences in LSTs in a semi-arid region in the city of Jaipur, where zones include rural and urban areas that encircle the Jhalana Reserve Forest (JRF). After deriving LSTs from remotely sensed thermal bands of Landsat satellites&rsquo; Multi-spectral datasets, we found that there is a significant difference in LST (p &lt; 0.01) among the zones. In addition, LSTs were found to be significantly lower in JRF compared to Urban and Rural areas in all seasons and all study years, which indicates the urban cooling effect due to the presence of the forest. Nevertheless, summer LSTs have warmed with a mean difference of 4.8 &deg;C between 2000 and 2020. Therefore, our study supports the promotion of Urban Forests, especially in semi-arid zones, for inculcating LST regulation ecosystem services to enrich and enhance the standard of living of the human population

Sclerosing liposarcoma of the anterior mediastinum: An unusual case

Liposarcomas are extremely rare in the mediastinum. Patients usually present late due to the compressive effect of the tumor on the adjacent structures. Severity of the symptoms depend mainly on the size of the tumor and the structure it infiltrates. Well differentiated slow growing liposarcomas are the most common ones in the mediastinum followed by dedifferentiated and poorly differentiated ones. These tumors have bad prognosis because of incomplete surgical excision due to its inaccessible location. Hence these patients should be kept under close follow up because of high recurrent rates. Here we are presenting a rare case of anterior mediastinal sclerosing liposarcoma in a 77 year old male

Prevalence and Short-Term Clinical Outcome of Mobile Thrombi Detected on Transvenous Leads in Patients Undergoing Lead Extraction.

This study sought to prospectively evaluate the prevalence, risk factors, and short-term major clinical outcomes of mobile thrombus detected on transvenous leads in patients undergoing lead extraction.The prevalence and clinical significance of thrombus on transvenous leads in patients undergoing lead extraction is not well characterized.Consecutive patients undergoing transvenous lead extraction for noninfectious indications were enrolled. Preoperative transesophageal echocardiograms were performed prospectively for all patients to examine for mobile thrombus. Anticoagulation was not started for thrombus unless other indications were present. Clinical endpoints of mortality and cardiovascular morbidity (symptomatic pulmonary embolism, myocardial infarction, or cerebrovascular accident) were assessed at a minimum of 2-month follow-up.A total of 108 patients underwent lead extraction for noninfectious indications. Lead thrombi were detected in 20 (18.5%) patients and all were &lt;2 cm. Clinical and lead characteristics were not associated with formation of lead thrombi, except for younger patient age. In patients with detected thrombi, there were no short-term deaths, symptomatic pulmonary embolisms, or myocardial infarctions, except 1 patient with a stroke 3 months after lead extraction (7% vs. 5%; p = 1.00). Median follow-up was 9 months.Mobile thrombi on transvenous leads are commonly found in patients referred for transvenous lead extraction and are rarely associated with acute major adverse outcomes. Careful extraction of leads with small incidentally detected thrombi can likely be performed without major acute clinical sequelae. Larger studies with longer follow-up are needed to further assess the long-term clinical significance of lead thrombi