Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Atlas of modern dinoflagellate cyst distribution based on 2405 data points

Dinoflagellate cysts are useful for reconstructing upper water conditions. For adequate reconstructions detailed information is required about the relationship between modern day environmental conditions and the geographic distribution of cysts in sediments. This Atlas summarises the modern global distribution of 71 organic-walled dinoflagellate cyst species. The synthesis is based on the integration of literature sources together with data of 2405 globally distributed surface sediment samples that have been prepared with a comparable methodology and taxonomy. The distribution patterns of individual cyst species are being compared with environmental factors that are known to influence dinoflagellate growth, gamete production, encystment, excystment and preservation of their organic-walled cysts: surface water temperature, salinity, nitrate, phosphate, chlorophyll-a concentrations and bottom water oxygen concentrations. Graphs are provided for every species depicting the relationship between seasonal and annual variations of these parameters and the relative abundance of the species. Results have been compared with previously published records; an overview of the ecological significance as well as information about the seasonal production of each individual species is presented.The relationship between the cyst distribution and variation in the aforementioned environmental parameters was analysed by performing a canonical correspondence analysis. All tested variables showed a positive relationship on the 99% confidence level. Sea-surface temperature represents the parameter corresponding to the largest amount of variance within the dataset (40%) followed by nitrate, salinity, phosphate and bottom-water oxygen concentration, which correspond to 34%, 33%, 25% and 24% of the variance, respectively. Characterisations of selected environments as well as a discussion about how these factors could have influenced the final cyst yield in sediments are included