A Gene-Based Association Method for Mapping Traits Using Reference Transcriptome Data

Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual’s genetic profile and correlates ‘imputed’ gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. Genetically regulated gene expression is estimated using whole-genome tissue-dependent prediction models trained with reference transcriptome data sets. PrediXcan enjoys the benefits of gene-based approaches such as reduced multiple-testing burden and a principled approach to the design of follow-up experiments. Our results demonstrate that PrediXcan can detect known and new genes associated with disease traits and provide insights into the mechanism of these associations

Genome evolution in the allotetraploid frog Xenopus laevis

To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of ???fossil??? transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.ope

Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Funder: Kennedy Trust Rheumatology Research Prize StudentshipFunder: DFG Cluster of Excellence “Precision Medicine in Chronic In-flammation” (PMI; ID: EXC2167)Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: “Ideas” Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNLFunder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421Abstract: Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS

A Hybrid Genetic Algorithm-Ratio DEA Approach for Assessing Sustainable Efficiency in Two-Echelon Supply Chains

Measuring sustainable efficiency is a wide research topic that has gained increased relevance over the course of the years, particularly in the field of supply chain management. In this paper, novel Data Envelopment Analysis—ratio data (DEA-R) models are used to assess sustainable efficiency in two-echelon supply chains based on endogenous factors. Genetic algorithms are employed to determine optimal productive weights for each echelon and the overall supply chain by taking into account the hidden correlation structures among them as expressed in non-linear multi-objective functions. A case study on 20 firefighting stations is presented to illustrate the approach proposed and its accuracy for decision-making, as long as the issues of pseudo inefficiency and over estimation of efficiency scores are mitigated. Results indicate that the method proposed is capable of reducing efficiency estimation biases due to endogenous sustainable factors by yielding overall scores lower than or equal to the product of the efficiencies of the individual stages

The Effect of Chamomile Tea versus Black Tea on Glycemic Control and Blood Lipid Profiles in Depressed Patients with Type 2 Diabetes: A Randomized Clinical Trial

Background: According to traditional beliefs, chamomile products have anti-depression effect. The aim of this study was to investigate the effects of chamomile tea on glycemic control, depression status and lipid profiles in type 2 diabetes (T2D) with depression. Methods: This randomized clinical trial was carried out on 74 depressed patients with T2D. Participants were randomly divided into two 37-people groups, chamomile tea (CG) and black tea group (BG). The CG received 3 cups of chamomile tea daily and the BG received 3 cups of black tea daily half an hour after meals for 12 weeks. To examine the status of depression, Beck II test was utilized. Anthropometric measurements, 24-h dietary recalls, glycosylated hemoglobin A1c (HbA1c) and blood lipids profile were measured at the baseline and at the end of the intervention. Results: The HbA1c mean was significantly reduced in CG after the intervention, when compared with BG (7.15 &plusmn; 1.23% vs. 7.98 &plusmn; 1.76%, P = 0.02). In the same vein, the mean changes in CG and BG were -0.74 &plusmn; 1.29 and 0.04 &plusmn; 1.07 (P = 0.006), respectively. No significant changes were observed in mean of serum lipids within and between groups. The Beck score also showed a significant reduction in the CG after the intervention (P < 0.001) and also, the mean changes showed a significant difference between the two groups. Conclusions: The results of this study demonstrated that drinking three cups of chamomile tea daily for 12 weeks by T2D suffering from depression lead to improve glycemic control and depression state. Therefore, drinking this kind of tea by these patients is recommende