Exploring Lead loci shared between schizophrenia and Cardiometabolic traits.

Individuals with schizophrenia (SCZ) have, on average, a 10- to 20-year shorter expected life span than the rest of the population, primarily due to cardiovascular disease comorbidity. Genome-wide association studies (GWAS) have previously been used to separately identify common variants in SCZ and cardiometabolic traits. However, genetic variants jointly influencing both traits remain to be fully characterised. To assess overlaps (if any) between the genetic architecture of SCZ and cardiometabolic traits, we used conditional false discovery rate (FDR) and local genetic correlation statistical framework analyses. A conjunctional FDR was used to identify shared genetic traits between SCZ and cardiometabolic risk factors. We identified 144 genetic variants which were shared between SCZ and body mass index (BMI), and 15 variants shared between SCZ and triglycerides (TG). Furthermore, we discovered four novel single nucleotide polymorphisms (SNPs) (rs3865350, rs9860913, rs13307 and rs9614186) and four proximate genes (DERL2, SNX4, LY75 and EFCAB6) which were shared by SCZ and BMI. We observed that the novel genetic variant rs13307 and the most proximate gene LY75 exerted potential effects on SCZ and BMI comorbidity. Also, we observed a mixture of concordant and opposite direction associations with shared genetic variants. We demonstrated a moderate to high genetic overlap between SCZ and cardiometabolic traits associated with a pattern of bidirectional associations. Our data suggested a complex interplay between metabolism-related gene pathways in SCZ pathophysiology

BreakTrans: Uncovering the genomic architecture of gene fusions

Producing gene fusions through genomic structural rearrangements is a major mechanism for tumor evolution. Therefore, accurately detecting gene fusions and the originating rearrangements is of great importance for personalized cancer diagnosis and targeted therapy. We present a tool, BreakTrans, that systematically maps predicted gene fusions to structural rearrangements. Thus, BreakTrans not only validates both types of predictions, but also provides mechanistic interpretations. BreakTrans effectively validates known fusions and discovers novel events in a breast cancer cell line. Applying BreakTrans to 43 breast cancer samples in The Cancer Genome Atlas identifies 90 genomically validated gene fusions. BreakTrans is available at http://bioinformatics.mdanderson.org/main/BreakTran

Neural Activation During Tonic Pain and Interaction Between Pain and Emotion in Bipolar Disorder: An fMRI Study

Objective: Pain and affective disorders have clear clinical relevance; however, very few studies have investigated the association between pain and bipolar disorder. This study investigated the brain activity of patients with bipolar disorder (BPs) undergoing tonic pain and assessed the interaction between pain and emotion.Methods: Ten BPs and ten healthy controls (HCs) were exposed to emotional pictures (positive, neutral, or negative), tonic pain only (pain session), and emotional pictures along with tonic pain (combined session). A moderate tonic pain was induced by the infusion of hypertonic saline (5% NaCl) into the right masseter muscle with a computer-controlled system. Whole-brain blood oxygenation level dependent (BOLD) signals were acquired using 3T functional resonance imaging (fMRI).Results: Ten BPs and ten healthy participants were included in the final analysis. During the pain session, BPs accepted more saline, but showed lower pain rating scores than HCs. When experiencing pain, BPs showed a significant decrease in the BOLD signal in the bilateral insula, left inferior frontal gyrus (IFG), and left cerebellum as compared with HCs. In the combined session, the activated regions for positive mood (pain with positive mood > baseline) in BPs were the left cerebellum, right temporal gyrus, and left occipital gyrus; the activated regions for negative mood (pain with negative mood > baseline) were the right occipital gyrus, left insula, left IFG, and bilateral precentral gyrus.Conclusions: This study presents the preliminary finding of the interaction between pain and emotion in BPs. BPs exhibited lower sensitivity to pain, and the activation of insula and IFG may reflect the interaction between emotion and pain stimulus

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Problematic Internet Use, Non-Medical Use of Prescription Drugs, and Depressive Symptoms among Adolescents: A Large-Scale Study in China

This large-scale study aimed to test, among Chinese adolescents, the association between problematic Internet use (PIU), non-medical use of prescription drugs (NMUPD), and depressive symptoms, as well as the mediating effects of NMUPD on the associations above. This study used the data from the 2017 National School-based Chinese Adolescents Health Survey, and 24,345 students&rsquo; questionnaires qualified for the analyses. Generalized linear mixed models and path models were performed. In the models without mediation, PIU was associated with depressive symptoms (unstandardized &beta; estimate = 0.26, 95% CI = 0.25&ndash;0.27); frequent use of opioid or sedative was also related to depressive symptoms (unstandardized &beta; estimate for opioid = 2.77, 95% CI = 1.90&ndash;3.63; unstandardized &beta; estimate for sedative = 4.45, 95% CI = 3.02&ndash;5.88). Additionally, the results of the path models indicated that opioid misuse partially mediated the association between PIU and depressive symptoms. PIU and opioid/sedative misuse were related to the increased risk of depressive symptoms, respectively. The association above might be complicated, and PIU may elevate the risk of opioid or sedative misuse and depressive symptoms, which in turn could worsen the situation of PIU and vice versa. Multidisciplinary health intervention programs to prevent adolescents involving in PIU, as well as NMPUD, are recommended to be provided

Light Spatial Distribution in the Canopy and Crop Development in Cotton

The partitioning of light is very difficult to assess, especially in discontinuous or irregular canopies. The aim of the present study was to analyze the spatial distribution of photosynthetically active radiation (PAR) in a heterogeneous cotton canopy based on a geo-statistical sampling method. Field experiments were conducted in 2011 and 2012 in Anyang, Henan, China. Field plots were arranged in a randomized block design with the main plot factor representing the plant density. There were 3 replications and 6 densities used in every replicate. The six plant density treatments were 15,000, 33,000, 51,000, 69,000, 87,000 and 105,000 plants ha(-1). The following results were observed: 1) transmission within the canopy decreased with increasing density and significantly decreased from the top to the bottom of the canopy, but the greatest decreases were observed in the middle layers of the canopy on the vertical axis and closing to the rows along the horizontal axis; 2) the transmitted PAR (TPAR) of 6 different cotton populations decreased slowly and then increased slightly as the leaves matured, the TPAR values were approximately 52.6-84.9% (2011) and 42.7-78.8% (2012) during the early cotton developmental stage, and were 33.9-60.0% (2011) and 34.5-61.8% (2012) during the flowering stage; 3) the Leaf area index (LAI) was highly significant exponentially correlated (R-2 = 0.90 in 2011, R-2 = 0.91 in 2012) with the intercepted PAR (IPAR) within the canopy; 4) and a highly significant linear correlation (R-2 = 0.92 in 2011, R-2 = 0.96 in 2012) was observed between the accumulated IPAR and the biomass. Our findings will aid researchers to improve radiation-use efficiency by optimizing the ideotype for cotton canopy architecture based on light spatial distribution characteristics

Le Peuple : organe quotidien du syndicalisme

26 avril 19361936/04/26 (A16,N5576)-1936/04/26