Density-functional embedding using a plane-wave basis

The constrained electron density method of embedding a Kohn-Sham system in a substrate system (first described by P. Cortona, Phys. Rev. B {\bf 44}, 8454 (1991) and T.A. Wesolowski and A. Warshel, J. Phys. Chem {\bf 97}, 8050 (1993)) is applied with a plane-wave basis and both local and non-local pseudopotentials. This method divides the electron density of the system into substrate and embedded electron densities, the sum of which is the electron density of the system of interest. Coupling between the substrate and embedded systems is achieved via approximate kinetic energy functionals. Bulk aluminium is examined as a test case for which there is a strong interaction between the substrate and embedded systems. A number of approximations to the kinetic-energy functional, both semi-local and non-local, are investigated. It is found that Kohn-Sham results can be well reproduced using a non-local kinetic energy functional, with the total energy accurate to better than 0.1 eV per atom and good agreement between the electron densities.Comment: 11 pages, 4 figure

Evaluating the contribution of rare variants to type 2 diabetes and related traits using pedigrees

A major challenge in evaluating the contribution of rare variants to complex disease is identifying enough copies of the rare alleles to permit informative statistical analysis. To investigate the contribution of rare variants to the risk of type 2 diabetes (T2D) and related traits, we performed deep whole-genome analysis of 1,034 members of 20 large Mexican-American families with high prevalence of T2D. If rare variants of large effect accounted for much of the diabetes risk in these families, our experiment was powered to detect association. Using gene expression data on 21,677 transcripts for 643 pedigree members, we identified evidence for large-effect rare-variant cis-expression quantitative trait loci that could not be detected in population studies, validating our approach. However, we did not identify any rare variants of large effect associated with T2D, or the related traits of fasting glucose and insulin, suggesting that large-effect rare variants account for only a modest fraction of the genetic risk of these traits in this sample of families. Reliable identification of large-effect rare variants will require larger samples of extended pedigrees or different study designs that further enrich for such variants

Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

10.1371/journal.pgen.1004876PLoS ONE111e100487