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

Ionization of deep impurities by far-infrared radiation

An analysis is made of the ionization of deep impurity centers by high-intensity far-infrared and submillimeter-wavelength radiation, with photon energies tens of times lower than the impurity ionization energy. Within a broad range of intensities and wavelengths, terahertz electric fields of the exciting radiation act as a dc field. Under these conditions, deep-center ionization can be described as multiphonon-assisted tunneling, in which carrier emission is accompanied by defect tunneling in configuration space and electron tunneling in the electric field. The field dependence of the ionization probability permits one to determine the defect tunneling times and the character of the defect adiabatic potentials. The ionization probability deviates from the field dependence e(E)}exp(E2/Ec 2) (where E is the wave field, and Ec is a characteristic field) corresponding to multiphonon-assisted tunneling ionization in relatively low fields, where the defects are ionized through the Poole–Frenkel effect, and in very strong fields, where the ionization is produced by direct tunneling without thermal activation. The effects resulting from the high radiation frequency are considered and it is shown that, at low temperatures, they become dominant