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Search: WFRF:(Agarwal PK)

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  • 2021
  • swepub:Mat__t
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  • Acosta-Herrera, M, et al. (author)
  • Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases
  • 2019
  • In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:3, s. 311-319
  • Journal article (peer-reviewed)abstract
    • Immune-mediated inflammatory diseases (IMIDs) are heterogeneous and complex conditions with overlapping clinical symptoms and elevated familial aggregation, which suggests the existence of a shared genetic component. In order to identify this genetic background in a systematic fashion, we performed the first cross-disease genome-wide meta-analysis in systemic seropositive rheumatic diseases, namely, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and idiopathic inflammatory myopathies.MethodsWe meta-analysed ~6.5 million single nucleotide polymorphisms in 11 678 cases and 19 704 non-affected controls of European descent populations. The functional roles of the associated variants were interrogated using publicly available databases.ResultsOur analysis revealed five shared genome-wide significant independent loci that had not been previously associated with these diseases: NAB1, KPNA4-ARL14, DGQK, LIMK1 and PRR12. All of these loci are related with immune processes such as interferon and epidermal growth factor signalling, response to methotrexate, cytoskeleton dynamics and coagulation cascade. Remarkably, several of the associated loci are known key players in autoimmunity, which supports the validity of our results. All the associated variants showed significant functional enrichment in DNase hypersensitivity sites, chromatin states and histone marks in relevant immune cells, including shared expression quantitative trait loci. Additionally, our results were significantly enriched in drugs that are being tested for the treatment of the diseases under study.ConclusionsWe have identified shared new risk loci with functional value across diseases and pinpoint new potential candidate loci that could be further investigated. Our results highlight the potential of drug repositioning among related systemic seropositive rheumatic IMIDs.
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  • Agarwal, PK, et al. (author)
  • Box-trees and R-trees with near-optimal query time
  • 2002
  • In: Discrete & Computational Geometry. - : Springer Science and Business Media LLC. - 0179-5376 .- 1432-0444. ; 28:3, s. 291-312
  • Journal article (peer-reviewed)abstract
    • A box-tree is a bounding-volume hierarchy that uses axis-aligned boxes as bounding volumes. The query complexity of a box-tree with respect to a given type of query is the maximum number of nodes visited when answering such a query. We describe several new algorithms for constructing box-trees with small worst-case query complexity with respect to queries with axis-parallel boxes and with points. We also prove lower bounds on the Worst-case query complexity for box-trees, which show that our results are optimal or close to optimal. Finally, we present algorithms to convert box-trees to R-trees, resulting in R-trees with (almost) optimal query complexity.
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