Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations.
Background Despite evidence from twin and family studies for an important contribution of genetic factors to both childhood and adult onset psychiatric disorders, identifying robustly associated specific DNA variants has proved challenging. In the pregenomics era the genetic architecture (number, frequency and effect size of risk variants) of complex genetic disorders was unknown. Empirical evidence for the genetic architecture of psychiatric disorders is emerging from the genetic studies of the last 5 years. Methods and scope We review the methods investigating the polygenic nature of complex disorders. We provide mini‐guides to genomic profile (or polygenic) risk scoring and to estimation of variance (or heritability) from common SNP s; a glossary of key terms is also provided. We review results of applications of the methods to psychiatric disorders and related traits and consider how these methods inform on missing heritability, hidden heritability and still‐missing heritability. Findings Genome‐wide genotyping and sequencing studies are providing evidence that psychiatric disorders are truly polygenic, that is they have a genetic architecture of many genetic variants, including risk variants that are both common and rare in the population. Sample sizes published to date are mostly underpowered to detect effect sizes of the magnitude presented by nature, and these effect sizes may be constrained by the biological validity of the diagnostic constructs. Conclusions Increasing the sample size for genome wide association studies of psychiatric disorders will lead to the identification of more associated genetic variants, as already found for schizophrenia. These loci provide the starting point of functional analyses that might eventually lead to new prevention and treatment options and to improved biological validity of diagnostic constructs. Polygenic analyses will contribute further to our understanding of complex genetic traits as sample sizes increase and as sample resources become richer in phenotypic descriptors, both in terms of clinical symptoms and of nongenetic risk factors.
Indian forests, having sixteen types of vegetation, provide various ecosystem services. Forests reduce water erosion of soil, reduce floods and conserve low river flow during dry seasons. Present study estimated annual sedimentation, texture, soil organic carbon control service of forests of India using the Revised Universal Soil Loss Equation (RUSLE) and Sediment Delivery Ratio (SDR) approach through GIS technique along with identifying important drivers responsible for erosion in forests. The soil erosion control service was based on five factors viz., rainfall erosivity, soil erodibility, slope, crop management, conservation practice factor and SDR across the various forest dominated river basins. Geo-detector modelling was performed to evaluate environmental drivers responsible for soil erosion. Valuation of soil control service of the India's forests was estimated based on damage and replacement cost method. Annual soil loss rate was maximum in Tropical Thorn Forest and in Ganga River basin. Maximum sediment control and SOC conservation against the soil erosion control service by India' forests were due to Tropical Dry Deciduous Forest with a total annual sedimentation control and SOC conservation of 33,056,560 tonnes and 3,31,115.06 tonnes, respectively. The conservative estimate of the economic value of soil conservation service by the forests of India was US$ 535.6 M with an average of 4.40 US$ ha−1 and a maximum share of value for Tropical Dry Deciduous Forest i.e. 294.18 million US$ and average maximum value for Littoral and Swamp Forest (28.91 US$ ha−1). The soil erosion in Tropical and Sub-tropical Forest was influenced by the interactive effects between NDVI and Bulk Density. In contrast, soil erosion in the temperate and alpine area was influenced by anthropogenic activity in combination with climatic factors. Present study accounts the role of India's forests for the soil conservation service and may provide inputs to implement forest and reservoir management strategies besides providing information for Integrated Watershed management and Catchment Treatment Plans.
Abstract Post-traumatic stress disorder (PTSD) selectively develops in some individuals exposed to a traumatic event. Genetic and epigenetic changes in glucocorticoid pathway sensitivity may be essential for understanding individual susceptibility to PTSD. This study focuses on PTSD markers in the glucocorticoid pathway, spotlighting glucocorticoid-induced leucine zipper (GILZ), a transcription factor encoded by the gene Tsc22d3 on the X chromosome. We propose that GILZ uniquely “quantifies” exposure to stressors experienced from late gestation to adulthood and that low levels of GILZ predispose individuals to PTSD in males only. GILZ mRNA and methylation were measured in 396 male and female human blood samples from the Grady Trauma Project cohort (exposed to multiple traumatic events). In mice, changes in glucocorticoid pathway genes were assessed following exposure to stressors at distinct time points: (i) CRF-induced prenatal stress ( CRF-induced PNS) with, or without, additional exposure to (ii) PTSD induction protocol in adulthood, which induces PTSD-like behaviors in a subset of mice. In humans, the number of traumatic events correlated negatively with GILZ mRNA levels and positively with % methylation of GILZ in males only. In male mice, we observed a threefold increase in the number of offspring exhibiting PTSD-like behaviors in those exposed to both CRF-induced PNS and PTSD induction. This susceptibility was associated with reduced GILZ mRNA levels and epigenetic changes, not found in females. Furthermore, virus-mediated shRNA knockdown of amygdalar GILZ increased susceptibility to PTSD. Mouse and human data confirm that dramatic alterations in GILZ occur in those exposed to a stressor in early life, adulthood or both. Therefore, GILZ levels may help identify at-risk populations for PTSD prior to additional traumatic exposures.
Annotation of genes with transcription start sites (TSS) near epigenetic clock CpGs and their expression changes in response to DEX. Gene annotation was based on [43]. (XLSX 26 kb)
Abstract Objective Over 90% of suicide attempters have a psychiatric diagnosis, however twin and family studies suggest that the genetic etiology of suicide attempt (SA) is partially distinct from that of the psychiatric disorders themselves. Here, we present the largest genome-wide association study (GWAS) on suicide attempt using major depressive disorder (MDD), bipolar disorder (BIP) and schizophrenia (SCZ) cohorts from the Psychiatric Genomics Consortium. Method Samples comprise 1622 suicide attempters and 8786 non-attempters with MDD, 3264 attempters and 5500 non-attempters with BIP and 1683 attempters and 2946 non-attempters with SCZ. SA GWAS were performed comparing attempters to non-attempters in each disorder followed by meta-analysis across disorders. Polygenic risk scoring investigated the genetic relationship between SA and the psychiatric disorders. Results Three genome-wide significant loci for SA were found: one associated with SA in MDD, one in BIP, and one in the meta-analysis of SA in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and i PSYCH. Polygenic risk scores for major depression were significantly associated with SA in MDD (P=0.0002), BIP (P=0.0006) and SCZ (P=0.0006). Conclusions This study provides new information on genetic associations and the genetic etiology of SA across psychiatric disorders. The finding that polygenic risk scores for major depression predict suicide attempt across disorders provides a possible starting point for predictive modelling and preventative strategies. Further collaborative efforts to increase sample size hold potential to robustly identify genetic associations and gain biological insights into the etiology of suicide attempt.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Falls after elective inpatient surgical procedures are common and have physical, emotional, and financial consequences. Close interactions between patients and health care teams before and after surgical procedures may offer opportunities to address modifiable risk factors associated with falls.
Objective
To assess whether a multicomponent intervention that incorporates education, home medication review, and home safety assessment is associated with reductions in the incidence of falls after elective inpatient surgical procedures.
Design, Setting, and Participants
This prospective propensity score–matched cohort study was a prespecified secondary analysis of data from the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized clinical trial, which was conducted at a single academic medical center between January 16, 2015, and May 7, 2018. Patients in the intervention group of the present study were enrolled in either arm of the ENGAGES clinical trial. Patients in the control group were selected from the Systematic Assessment and Targeted Improvement of Services Following Yearly Surgical Outcomes Surveys prospective observational cohort study, which created a registry of patient-reported postoperative outcomes at the same single center. The propensity score–matched cohort in the present study included 1396 patients (698 pairs) selected from a pool of 2013 eligible patients. All patients underwent elective surgical procedures with general anesthesia and had a hospital stay of 2 or more days. Data were analyzed from January 2, 2020, to January 11, 2022.
Interventions
The multicomponent safety intervention (offered to all patients in the ENGAGES clinical trial) included patient education on fall prevention techniques, home medication review by a geriatric psychiatrist (with communication of recommended changes to the surgeon), a self-administered home safety assessment, and targeted occupational therapy home visits with home hazard removal (offered to patients with a preoperative history of falls).
Main Outcomes and Measures
The primary outcome was patient-reported falls within 1 year after an elective inpatient surgical procedure. The secondary outcome was quality of life 1 year after an elective surgical procedure, which was measured using the physical and mental composite summary scores on the Veterans RAND 12-item health survey (score range, 0-100 points, with 0 indicating lowest quality of life and 100 indicating highest quality of life).
Results
Among 1396 patients, the median age was 69 years (IQR, 64-75 years), and 739 patients (52.9%) were male. With regard to race, 5 patients (0.4%) were Asian, 97 (6.9%) were Black or African American, 2 (0.1%) were Native Hawaiian or Pacific Islander, 1237 (88.6%) were White, 3 (0.2%) were of other race, and 52 (3.7%) were of unknown race; with regard to ethnicity, 12 patients (0.9%) were Hispanic or Latino, 1335 (95.6%) were non-Hispanic or non-Latino, and 49 (3.5%) were of unknown ethnicity. Adherence to individual intervention components was modest (from 22.9% for completion of the self-administered home safety assessment to 28.2% for implementation of the geriatric psychiatrist's recommended medication changes). Falls within 1 year after surgical procedures were reported by 228 of 698 patients (32.7%) in the intervention group and 225 of 698 patients (32.2%) in the control group. No significant difference was found in falls between the 2 groups (standardized risk difference, 0.4%; 95% CI, −4.5% to 5.3%). After adjusting for preoperative quality of life, patients in the intervention group had higher physical composite summary scores (3.8 points; 95% CI, 2.4-5.1 points) and higher mental composite summary scores (5.7 points; 95% CI, 4.7-6.7 points) at 1 year compared with patients in the control group.
Conclusions and Relevance
In this cohort study, a multicomponent safety intervention was not associated with reductions in falls within the first year after an elective surgical procedure; however, an increase in quality of life at 1 year was observed. These results suggest a need for other interventions, such as those designed to increase adherence, to lower the incidence of falls after surgical procedures.
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