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  • Berndt, Sonja I., et al. (författare)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • Ingår i: Nature Genetics. - 1061-4036. ; 45:5, s. 501-U69
  • Tidskriftsartikel (refereegranskat)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
  • Randall, Joshua C, et al. (författare)
  • Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits
  • 2013
  • Ingår i: PLoS Genetics. - Public Library Science. - 1553-7390. ; 9:6, s. e1003500
  • Tidskriftsartikel (refereegranskat)abstract
    • Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - 1061-4036. ; 45:11, s. 1345-
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
  • Wain, Louise V., et al. (författare)
  • Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
  • 2011
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036. ; 43:10, s. 1005-U122
  • Tidskriftsartikel (refereegranskat)abstract
    • Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.
  • Willer, Cristen J., et al. (författare)
  • Discovery and refinement of loci associated with lipid levels
  • 2013
  • Ingår i: Nature Genetics. - 1061-4036. ; 45:11, s. 1274-1283
  • Tidskriftsartikel (refereegranskat)abstract
    • Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
  • Abdullah, Syed Md Jakaria, et al. (författare)
  • Towards Implementation of Virtual-Clustered Multiprocessor Scheduling in Linux
  • 2013
  • Ingår i: Proceedings of the 8th IEEE International Symposium on Industrial Embedded Systems, SIES 2013. - 9781479906581 ; s. 97-100
  • Konferensbidrag (refereegranskat)abstract
    • Cluster based multiprocessor scheduling can be seen as a hybrid approach combining benefits of both partitioned and global scheduling. Virtual clustering further enhances it by providing dynamic cluster resource allocation and applying hierarchical scheduling techniques. Over the years, the study of virtual cluster scheduling has been limited to theoretical analysis. In this paper, we present our initial ideas about implementing virtual cluster scheduling in Linux. The purpose of this implementation is twofold: (i) we would like to demonstrate the feasibility of its implementation in an operating system, without modifying the kernel source code, (ii) we present practical insights on the overhead of implementing this framework.
  • Afshar, Sara, et al. (författare)
  • Flexible Spin-Lock Model for Resource Sharing in Multiprocessor Real-Time Systems
  • 2014
  • Ingår i: 9th IEEE International SIES SIES'14. - Pisa, Italy.
  • Konferensbidrag (refereegranskat)abstract
    • Various approaches can be utilized upon resource locking for mutually exclusive resource access in multiprocessor platforms. So far two conventional approaches exist for dealing with tasks that are blocked on a global resource in a multiprocessor platform. Either the blocked task performs a busy wait, i.e. spins, at the highest priority level until the resource is released, or it is suspended. Although both approaches provide mutually exclusive access to resources, they can introduce long blocking delays to tasks, which may be unacceptable for many industrial applications. In this paper, we propose a general spinbased model for resource sharing in multiprocessor platforms in which the priority of the blocked tasks during spinning can be selected arbitrarily. Moreover, we provide the analysis for two selected spin-lock priorities and we show by means of a general comparison as well as specific examples that these solutions may provide a better performance for higher priority tasks.
  • Afshar, Sara, et al. (författare)
  • Integrating independently developed real-time applications on a shared multi-core architecture
  • 2012
  • Konferensbidrag (refereegranskat)abstract
    • The shift towards multi-core platforms has become inevitable from an industry perspective, therefore proper techniques are needed to deal with challenges related to this migration from single core architectures to a multi-core architecture. One of the main concerns for the system developers in this context is the migration of legacy real-time systems to multi-core architectures. To address this concern and to simplify migration, independently developed subsystems are abstracted with an interface, such that when working with multiple independently-developed subsystems to be integrated on a shared platform, one does not need to be aware of information or policies used in other subsystems in order to determine subsystem-level schedulability. Instead schedulability can be checked through their interfaces at the time of integration on a shared multi-core architecture. In this paper we propose a solution for the case where some of the independently-developed subsystems are distributed over more than one processor and we propose an approach to generate interfaces of subsystems that may share mutually exclusive resources.
  • Afshar, Sara, et al. (författare)
  • Resource Sharing among Prioritized Real-Time Applications on Multiprocessors
  • 2013
  • Konferensbidrag (refereegranskat)abstract
    • In this paper, we propose a new protocol for handling resource sharing among prioritized real-time applications composed on a multiprocessor platform. We propose an optimal priority assignment algorithm which assigns unique priorities to the applications based on information in their interfaces. We have performed experimental evaluations to compare the proposed protocol (called MSOS-Priority) to the current state of the art locking protocols under multiprocessor partitioned scheduling, i.e., MPCP, MSRP, FMLP, MSOS, and OMLP. The valuations show that MSOS-Priority mostly performs significantly better than alternative approaches.
  • Afshar, Sara, et al. (författare)
  • Resource Sharing under Multiprocessor Semi-Partitioned Scheduling
  • 2012
  • Ingår i: 18th IEEE International Conference on Embedded and Real-Time Computing Systems and Applications (RTCSA'12). - 978-1-4673-3017-6 ; s. 290-299
  • Konferensbidrag (refereegranskat)abstract
    • Semi-partitioned scheduling has become the subject of recent interest for multiprocessors due to better utilization results, compared to conventional global and partitioned scheduling algorithms. Under semi-partitioned scheduling, a major group of tasks are assigned to fixed processors while a low number of tasks are allocated to more than one processor. Various task assigning techniques have recently been proposed in a semi-partitioned environment. However, a synchronization mechanism for resource sharing among tasks in semi-partitioned scheduling has not yet been investigated. In this paper we propose and evaluate two methods for handling resource sharing under semi-partitioned scheduling in multiprocessor platforms. The main challenge addressed in this paper is to serve the resource requests of tasks that are assigned to different processors.
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