Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

RELAP5 based engineering simulator

The INEL Engineering Simulation Center was established in 1988 to provide a modern, flexible, state-of-the-art simulation facility. This facility and two of the major projects which are part of the simulation center, the Advance Test Reactor (ATR) engineering simulator project and the Experimental Breeder Reactor II (EBR-II) advanced reactor control system, have been the subject of several papers in the past few years. Two components of the ATR engineering simulator project, RELAP5 and the Nuclear Plant Analyzer (NPA), have recently been improved significantly. This paper will present an overview of the INEL Engineering Simulation Center, and discuss the RELAP5/MOD3 and NPA/MOD1 codes, specifically how they are being used at the INEL Engineering Simulation Center. It will provide an update on the modifications to these two codes and their application to the ATR engineering simulator project, as well as, a discussion on the reactor system representation, control system modeling, two phase flow and heat transfer modeling. It will also discuss how these two codes are providing desktop, stand-alone reactor simulation. 12 refs., 2 figs