IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach

The materhorn : Unraveling the intricacies of mountain weather

Emerging application areas such as air pollution in megacities, wind energy, urban security, and operation of unmanned aerial vehicles have intensified scientific and societal interest in mountain meteorology. To address scientific needs and help improve the prediction of mountain weather, the U.S. Department of Defense has funded a research effort\u2014the Mountain Terrain Atmospheric Modeling and Observations (MATERHORN) Program\u2014that draws the expertise of a multidisciplinary, multi-institutional, and multinational group of researchers. The program has four principal thrusts, encompassing modeling, experimental, technology, and parameterization components, directed at diagnosing model deficiencies and critical knowledge gaps, conducting experimental studies, and developing tools for model improvements. The access to the Granite Mountain Atmospheric Sciences Testbed of the U.S. Army Dugway Proving Ground, as well as to a suite of conventional and novel high-end airborne and surface measurement platforms, has provided an unprecedented opportunity to investigate phenomena of time scales from a few seconds to a few days, covering spatial extents of tens of kilometers down to millimeters. This article provides an overview of the MATERHORN and a glimpse at its initial findings. Orographic forcing creates a multitude of time-dependent submesoscale phenomena that contribute to the variability of mountain weather at mesoscale. The nexus of predictions by mesoscale model ensembles and observations are described, identifying opportunities for further improvements in mountain weather forecasting