International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Enhancing discovery of genetic variants for posttraumatic stress disorder through integration of quantitative phenotypes and trauma exposure information

Background Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods

Potential causal association between gut microbiome and posttraumatic stress disorder

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms

Оптимизация конструкции захвата для детали «Барабан»

Грузозахватные приспособления обычно применяются при производстве работ по подъему и перемещению грузов с применением грузоподъемных машин. Использование приспособлений позволяет реализовать максимальное удобство и безопасность производственного процесса. Грузозахватные приспособления конструируются для определенного этапа технологического процесса, для конкретного изделия. При проектировании таких приспособлений необходимо учитывать основные показатели оптимальности конструкции: прочность, надежность, простота, удобство и безопасность при эксплуатации, эргономичность. Кроме того, нужно стремиться к наименьшей массе и, соответственно, металлоемкости захвата. Конструкция грузозахватного приспособления, в основном, будет зависеть от назначенных технологом поверхностей, за которые можно крепиться и от максимальной высоты подъема крюка крана. В статье описана задача по конструированию захвата для детали «Барабан¬ в новом технологическом процессе. Рассмотрена конструкция существующего захвата, взятого за прототип. Приведен анализ различных вариантов конструктивных решений, созданных в процессе проектирования. Выбран вариант конструкции захвата, который в наибольшей степени соответствует требованиям технического задания. Конструкция этого модернизированного приспособления представляет собой захват с тремя лапами, удерживающими деталь, и подвес в виде траверсы. Разработанная конструкторская документация утверждена производством и отделом промышленной безопасности

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. © 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Potential causal association between gut microbiome and posttraumatic stress disorder

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms

Recovery of rare earths from bauxite residue leachates by functionalised sorbents

Bauxite residue, better known as red mud, is a waste product of the alumina industry, but with many unexploited values. The estimated inventory of bauxite residue in operating and closed alumina refineries reaches the value of several billion of tonnes. Stockpiling of huge amounts of residue can create environmental problems. Bauxite residue comprises iron, aluminium, titanium, sodium and even more interestingly, valuable rare-earth elements (REEs). Although a lot of research has been done on bauxite residue valorisation, to date there are no large-scale applications of bauxite residue yet. The REEs, and scandium in particular, are generally more enriched in residues originating from karst bauxites. Interestingly, bauxites found in the southern region of Europe belong to the group of karst bauxites. Europe currently has no operating REE mine, although these elements are getting an increasing role as materials for the transition to cleaner energy and the production of high-tech devices. In this PhD thesis sorbents were synthesised and investigated for the recovery of REEs from bauxite residue leachates. The leachates can be prepared by direct leaching of bauxite residue with mineral acids, or as a processing step after recovery of other valuable metals. The leachates typically comprise low concentrations of REEs, whereas base elements like iron or aluminium are concentrated. Liquid-solid extraction is a suitable method for recovery of elements from dilute streams. This process requires sorbents selective for elements of interest. Supported ionic liquid phases (SILPs) and crystalline zirconium-phosphate (α-ZrP) were synthesised, characterised and examined for the REEs recovery and separation from other element present in bauxite residue leachates. Moreover, hybrid materials prepared by grafting of short n-alkyl chains (ethyl, n-propyl and n-butyl) to titanium(IV) phosphate functionalised mesoporous MCM-41 silica were tested for mutual separation of REEs. Two routes for SILPs preparation were investigated: physical impregnation of ionic liquids on a solid support or chemical immobilisation by covalent bonding of the ionic liquid anion to the solid support. The SILP betainium sulfonyl(trifluoromethanesulfonylimide) poly(styrene-co-divinylbenzene), [Hbet-STFSI-PS-DVB], prepared by covalent bonding of ionic liquid to the resin resulted in a sorbent suitable for scandium recovery. The SILP was tested batchwise to reveal its basic performance for scandium recovery from synthetic acidic solutions, such as selectivity, kinetics, influence of pH and sorption capacity. [Hbet-STFSI-PS-DVB] was packed in a column and detailed studies on REEs separation from base elements were performed under column operating conditions. [Hbet-STFSI-PS-DVB] performance for separation of REEs and the base elements in bauxite residue was evaluated with real acidic bauxite residue leachates. The leachates were obtained by direct leaching of bauxite residue by acids and by high-pressure leaching of a slag generated after smelting reduction of bauxite residue for iron recovery. In both cases, a proof-of-principle for the REEs recovery and separation from base elements by the [Hbet-STFSI-PS-DVB] was confirmed. The performance of [Hbet-STFSI-PS-DVB] was further evaluated in a simplified study with a simulated H2SO4 leachate. From this leachate, iron was selectively precipitated and the remaining solution was subsequently tested for the REEs recovery by the [Hbet-STFSI-PS-DVB]. After precipitating iron, scandium uptake from the sulfate media was boosted. Moreover, the purity of scandium obtained after column chromatography was superior to the purity obtained after ScPO4 precipitation. Furthermore, the selectivity for scandium over iron of several metal(IV) phosphates was investigated from acidic solutions. It was found that α-ZrP exhibits a strong affinity towards scandium, superior to other tested metal(IV) phosphates. Therefore scandium uptake by α-ZrP was investigated in depth. After evaluating batchwise its performance for scandium recovery, α-ZrP was packed in a column. Scandium separation by the α-ZrP column was examined with a leachate obtained by direct leaching of bauxite residue with HCl. A prominent selectivity for scandium over the vast majority of other elements present in bauxite residue was observed. Due to the small differences between the different REE, they are often recovered from leachates by liquid-liquid or liquid-solid extraction as a group of elements. Still, for certain applications their separation into individual elements is required. The grafted MCM-41 materials were examined for separation of mixtures of REEs. The separation between scandium and lanthanum was found to be remarkable, whereas neodymium and dysprosium separation was comparable to the separation obtained in liquid-liquid extractions with typical extractants such as tributyl phosphate (TBP).status: publishe