| 1. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Xiong, Binyu, et al.
(författare)
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A flow-rate-aware data-driven model of vanadium redox flow battery based on gated recurrent unit neural network
- 2023
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Ingår i: Journal of Energy Storage. - 2352-152X. ; 74
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Tidskriftsartikel (refereegranskat)abstract
- The vanadium redox flow battery (VRB) system involves complex multi-physical and multi-timescale interactions, where the electrolyte flow rate plays a pivotal role in both static and dynamic performance. Traditionally, fixed flow rates have been employed for operational convenience. However, in today's highly dynamic energy market environment, adjusting flow rates based on operating conditions can provide significant advantages for improving VRB energy conversion efficiency and cost-effectiveness. Unfortunately, incorporating the electrolyte flow rate into conventional multi-physical models is overly complex for VRB management and control systems, as real-time operations demand low-computational and low-complexity models for onboard functionalities. This paper introduces a novel data-driven approach that integrates flow rates into VRB modeling, enhancing data processing capabilities and prediction accuracy of VRB behaviors. The proposed model adopts a gated recurrent unit (GRU) neural network as its fundamental framework, exhibiting exceptional proficiency in capturing VRB's nonlinear voltage segments. The GRU network structure is carefully designed to optimize the predictive ability of the model, with flow rate considered as a crucial input parameter to account for its influence on VRB behavior. Model refinement involves analyzing well-designed simulation results obtained during VRB operations under various flow rates. Laboratory experiments were also designed and conducted, covering different conditions of currents and flow rates to validate the proposed data-driven modeling method. Comparative analyses were performed against several state-of-the-art algorithms, including equivalent circuit models and other data-driven models, demonstrating the superiority of the proposed GRU-based VRB model considering flow rates. Thanks to the GRU's outstanding capability in processing time series data, the proposed model delivers impressively accurate terminal voltage predictions with a low error margin of no more than 0.023 V (1.3%) under wide operating ranges. These results indicate the efficacy and robustness of the proposed approach, highlighting the novelty and significance of accounting for flow rates in accurate VRB modeling for management and control system design.
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| 3. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 4. |
- Takeuchi, Fumihiko, et al.
(författare)
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Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- 2018
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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| 5. |
- Zhang, Zengxin, et al.
(författare)
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Evaluating the non-stationary relationship between precipitation and streamflow in nine major basins of China during the past 50 years
- 2011
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Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694 .- 1879-2707. ; 409:1-2, s. 81-93
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, the trends of the annual streamflow and precipitation and cross correlations between them were analyzed in nine large river basins of China during 1956-2005. The results indicate that: (1) the annual mean streamflow decreases in arid and semi-arid regions of north China; however, increasing trends occur in south and Southwest China; (2) the annual streamflow and precipitation exhibit reasonable correlation in nine large river basins except those located in inland areas. The annual streamflow over most areas of China is fed by precipitation; however, the decline in streamflow is faster than the decreases of precipitation since 1970s in the arid and semi-arid regions of north China. The relationship between the annual precipitation and streamflow presents a non-stationary state in north China. This non-stationary relationship is strongly influenced by both human activities and precipitation changes; (3) a significant increase of water use might be the major factor responsible for the steeper decline in streamflow than in precipitation in Haihe River, Yellow River and Songliao River basins in north China. In inland river areas, increase of water use and actual evapotranspiration might result in decline in streamflow although precipitation has an increase tendency. This paper sheds light on the non-stationary relationship between annual precipitation and streamflow and possible underlying causes, which will be helpful for a better understanding of the changes of precipitation and streamflow in China at large scale and in other regions of the world.
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