Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups

Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85610 x 10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84 x 10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at similar to 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults

Preemption concepts, Rhealstone benchmark and scheduler analysis of linux 2.4

In this paper we examine the soft realtime capabilities of the Linux kernel 2.4 and realtime enhancements. We discuss and visualize in the form of PDLT (process dispatch latency time) diagrams how the MontaVista Preemption Patch 6 for Linux 2.4.2 preempts a Linux system call executing in kernel mode. In similar diagrams we show the effect of introducing Conditional Preemption Points, like Ingo Molnar´s and Andrew Morton´s Low Latency Patches do. To detect possible performance changes we measure some programs of the Rhealstone Benchmark on Linux kernels and variants. We examine the behaviour of the Linux scheduler when scheduling a SCHED FIFO process varying the number of SCHED OTHER load processes ready to run.

Time-critical tasks in Linux 2.6: Concepts to increase the preemptability of the Linux kernel

mutex, priority inversion, priority inheritance, scheduler, timing resolution In the new Linux 2.6 kernel some features that are important for time-critical tasks have been integrated. In Linux 2.6 the Preemptible Kernel Patch [6] has been integrated as a kernel configuration option. If selected Linux 2.6 kernel code can now be preempted, if a process of higher priority requires the processor. This is a very important feature for soft-realtime tasks. In Linux 2.6 the timer interrupt service routine is preset to be executed every 1 millisecond, ten times more often than in Linux 2.4, this means a 10 times higher timing precision in Linux 2.6, although some overhead. In Linux 2.4 the execution time of the scheduler depends on th