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- Young, William J., et al.
(author)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Journal article (peer-reviewed)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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- Björkdahl, Annika, et al.
(author)
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Spaces of Peace
- 2021
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In: The Oxford Handbook of Peacebuilding, Statebuilding, and Peace Formation. - : Oxford University Press. - 9780190904418 - 9780197576410 ; , s. 139-151
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Book chapter (peer-reviewed)abstract
- This chapter shows that war-making and peace-making “take place” and that sometimes the legacy of conflict obscures manifestations of peacebuilding. The analysis of a “bridge that divides” in the city of Mitrovica in northern Kosovo and a “wall that unites” in Belfast, Northern Ireland, casts light on the benefits that a spatial reading of peace can provide to understand the ways in which spatial infrastructures are lived by the people who use them. The process of space-making (the generation of meanings from a material location) will help explain the agency that emerges by the creators, users, and inhabitants of (post)conflict spaces.
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- Richmond, Oliver P., et al.
(author)
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The 'Field' in the Age of Intervention: Power, Legitimacy, and Authority Versus the 'Local'
- 2015
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In: Millennium. - : SAGE Publications. - 0305-8298. ; 44:1, s. 23-44
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Journal article (peer-reviewed)abstract
- This article highlights the semantic and socio-political meaning of the 'field' as it is used in both academic research and policy practices: as a geographic and material space related to forms of intervention in International Relations (IR), and not as a disciplinary space. We argue that the notion of the field' carries colonial baggage in terms of denoting 'backwardness' and conflictual practices, as well as legitimising the need for intervention by peacebuilding, statebuilding, and development actors located outside the field. We also show how academic practices have tended to create a semiotic frame in which the inhabitants of the research and intervention space are kept at a distance from the researcher, and discursively stripped of their agency. Along similar lines, policy-practice has reinforced the notion of the field as being in need of intervention, making it subject to external control. This article suggests that the agency of the inhabitants of the field has to be re-cognised and de-colonised so that political legitimacy can be recovered from 'intervention'.
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