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We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.

A density functional theory of the spatial distribution and biaxial nematic order of polymers of arbitrary length and rigidity inside a spherical cavity is proposed. The local order of different chain segments is considered as an alignment to a spatially varying director field of cylindrical symmetry. The steric interactions are taken into account in the second virial approximation. Polymer density and orientational order distributions inside the spherically cavity are the principal results. It was found that short and flexible polymers were located at the center of the sphere and were orientationaly disordered. Upon increasing polymer length and/or polymer rigidity, the location of the polymer was continuously shifted toward the surface of the spherical cavity and the polymer segments became gradually more aligned. Parameters have been selected to model the behavior of genomes in spherical viral capsids.

Nematic ordering is studied in solutions of rodlike macroions in the presence of monovalent salt ions. The correlation free energy of electrostatic interactions is calculated within the framework of the Debye-Hückel approach. The phase diagram of the system is obtained. We have shown that the addition of salt destroys the weakly ordered nematic phase which is stable at small polymer concentrations. On the other hand, the salt widens the region of the phase separation between the isotropic (or weakly ordered nematic) and the highly ordered nematic phases at high polymer concentrations. An explanation of these effects is proposed.