Re-circumscription of the mimosoid genus Entada including new combinations for all species of the phylogenetically nested Elephantorrhiza (Leguminosae, Caesalpinioideae, mimosoid clade)

Recent phylogenomic analyses of 997 nuclear genes support the long-held view that the genus Entada is congeneric with Elephantorrhiza. Entada is resolved as monophyletic only if the genus Elephantorrhiza is subsumed within it. The two genera were distinguished solely by relatively minor differences in the mode of dehiscence of the fruits (a craspedium separating into one-seeded endocarp segments in Entada versus a craspedium with the whole fruit valve breaking away from the persistent replum in Elephantorrhiza) and the craspedial fruit type itself provides a shared synapomorphy for the re-circumscribed Entada. Here, we provide a synopsis of Entada, including 11 new combinations in total, for the eight species, one subspecies and one variety previously placed in Elephantorrhiza, as well as a new combination for a subspecies of Entada rheedei Spreng. not previously dealt with when Entada pursaetha DC. was placed in synonymy. These new combinations are: Entada burkei (Benth.) S.A. O’Donnell & G.P. Lewis, comb. nov.; Entada elephantina (Burch.) S.A. O’Donnell & G.P. Lewis, comb. nov.; Entada goetzei (Harms) S.A. O’Donnell & G.P. Lewis, comb. nov.; Entada goetzei subsp. lata (Brenan & Brummitt) S.A. O’Donnell & G.P. Lewis, comb. nov.; Entada obliqua (Burtt Davy) S.A. O’Donnell & G.P. Lewis, comb. nov.; Entada praetermissa (J.H. Ross) S.A. O’Donnell & G.P. Lewis, comb. nov.; Entada rangei (Harms) S.A. O’Donnell & G.P. Lewis, comb. nov.; Entada rheedei subsp. sinohimalensis (Grierson & D.G. Long) S.A. O’Donnell & G.P. Lewis, comb. nov.; Entada schinziana (Dinter) S.A. O’Donnell & G.P. Lewis, comb. nov.; Entada woodii (E. Phillips) S.A. O’Donnell & G.P. Lewis, comb. nov.; and Entada woodii var. pubescens (E. Phillips) S.A. O’Donnell & G.P. Lewis, comb. nov. We provide a revised circumscription of the genus Entada which now comprises 40 species distributed pantropically, with the greatest diversity of species in tropical Africa. We present a complete taxonomic synopsis, including a map showing the global distribution of the genus and photographs showing variation amongst species in habit, foliage, flowers and fruits. A short discussion about extrafloral nectaries, mainly observed in the Madagascan species, is presented

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

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

A Staphylococcal GGDEF Domain Protein Regulates Biofilm Formation Independently of Cyclic Dimeric GMP ▿

Cyclic dimeric GMP (c-di-GMP) is an important biofilm regulator that allosterically activates enzymes of exopolysaccharide biosynthesis. Proteobacterial genomes usually encode multiple GGDEF domain-containing diguanylate cyclases responsible for c-di-GMP synthesis. In contrast, only one conserved GGDEF domain protein, GdpS (for GGDEF domain protein from Staphylococcus), and a second protein with a highly modified GGDEF domain, GdpP, are present in the sequenced staphylococcal genomes. Here, we investigated the role of GdpS in biofilm formation in Staphylococcus epidermidis. Inactivation of gdpS impaired biofilm formation in medium supplemented with NaCl under static and flow-cell conditions, whereas gdpS overexpression complemented the mutation and enhanced wild-type biofilm development. GdpS increased production of the icaADBC-encoded exopolysaccharide, poly-N-acetyl-glucosamine, by elevating icaADBC mRNA levels. Unexpectedly, c-di-GMP synthesis was found to be irrelevant for the ability of GdpS to elevate icaADBC expression. Mutagenesis of the GGEEF motif essential for diguanylate cyclase activity did not impair GdpS, and the N-terminal fragment of GdpS lacking the GGDEF domain partially complemented the gdpS mutation. Furthermore, heterologous diguanylate cyclases expressed in trans failed to complement the gdpS mutation, and the purified GGDEF domain from GdpS possessed no diguanylate cyclase activity in vitro. The gdpS gene from Staphylococcus aureus exhibited similar characteristics to its S. epidermidis ortholog, suggesting that the GdpS-mediated signal transduction is conserved in staphylococci. Therefore, GdpS affects biofilm formation through a novel c-di-GMP-independent mechanism involving increased icaADBC mRNA levels and exopolysaccharide biosynthesis. Our data raise the possibility that staphylococci cannot synthesize c-di-GMP and have only remnants of a c-di-GMP signaling pathway

Population demographics and risk factors of individual sites and for whole cohort.

§<p>Doctor Diagnosis of AO = presence of self reported prior diagnosis of either ever-asthma, or asthmatic bronchitis, or allergic bronchitis, or COPD, or emphysema, or chronic bronchitis. Data for Age, BMI, Packyears, and Spirometry results are expressed in mean(SD); All others are expressed as % of group(SE) and are weighted to the local population. BMI = Body-mass index;</p>†<p>% predicted values = maximum values/predicted values(NHANES)*100;</p>*<p>One-Way ANOVA, alpha = 0.05;</p>#<p>Chi-Square Test.</p>&<p>post bronchodilator responses: % change in FEV1 or FVC after bronchodilator relative to pre-bronchodilator value.</p

Determinants of bronchodilator responsiveness in forced expiratory volume in one second as % pre-bronchodilator value [%ΔFEV1i] –results from univariate and multivariate analyses of the whole cohort.

*<p>Standard estimates allow comparison between variables with different units. It is the expected change in bronchodilator response per 1 SD increase in the variable. After multivariate correction for confounding variables the ‘most powerful’ effect on BDRFEV1 is doctor diagnosis of current-asthma, followed by age, ever-smoking, use of respiratory drugs (any medication for breathing including nasal decongestant), and gender.These values are adjusted for all corivariates including site and for the proportion of Caucasian population in each site.</p

Logistic regression analysis of cohort without self-reported diagnosis of ever-asthma, COPD/Chronic bronchitis/Emphysema (n = 3508) showing risk [adjusted Odds ratio & 95% confidence intervals] of Symptoms with increasing post-bronchodilator change in forced expiratory volume in 1 sec % pre-bronchodilator value (%ΔFEV1i).

*<p>Variables for the first Quintile were used as the reference;</p><p>#Slope for trend was statistically different from the horizontal. Odds ratios and 95% CI adjusted for age, BMI, gender, usage of respiratory drugs (any medication for breathing including nasal decongestant), ever-smoking, site, and porpotion of Caucasian.</p

Logistic regression analysis of cohort without self-reported diagnosis of ever-asthma, COPD/Chronic bronchitis/Emphysema (n = 3378) showing risk [adjusted Odds ratio & 95% confidence intervals] of Symptoms with increasing post-bronchodilator change in forced vital capacity as % Pre-bronchodilator value (%ΔFVCi).

*<p>Variables for the first Quintile were used as the reference;</p><p>#Slope for trend was statistically different from the horizontal. Odds ratios and 95% CI adjusted for age, BMI, gender, usage of respiratory drugs (any medication for breathing including nasal decongestant), ever-smoking, site, and proportion of Caucasian.</p

High-throughput multimodal automated phenotyping (MAP) with application to PheWAS

© 2019 The Author(s). Objective: Electronic health records linked with biorepositories are a powerful platform for translational studies. A major bottleneck exists in the ability to phenotype patients accurately and efficiently. The objective of this study was to develop an automated high-throughput phenotyping method integrating International Classification of Diseases (ICD) codes and narrative data extracted using natural language processing (NLP). Materials and Methods: We developed a mapping method for automatically identifying relevant ICD and NLP concepts for a specific phenotype leveraging the Unified Medical Language System. Along with health care utilization, aggregated ICD and NLP counts were jointly analyzed by fitting an ensemble of latent mixture models. The multimodal automated phenotyping (MAP) algorithm yields a predicted probability of phenotype for each patient and a threshold for classifying participants with phenotype yes/no. The algorithm was validated using labeled data for 16 phenotypes from a biorepository and further tested in an independent cohort phenome-wide association studies (PheWAS) for 2 single nucleotide polymorphisms with known associations. Results: The MAP algorithm achieved higher or similar AUC and F-scores compared to the ICD code across all 16 phenotypes. The features assembled via the automated approach had comparable accuracy to those assembled via manual curation (AUCMAP 0.943, AUCmanual 0.941). The PheWAS results suggest that the MAP approach detected previously validated associations with higher power when compared to the standard PheWAS method based on ICD codes. Conclusion: The MAP approach increased the accuracy of phenotype definition while maintaining scalability, thereby facilitating use in studies requiring large-scale phenotyping, such as PheWAS