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- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 3. |
- Figueroa, Jonine D., et al.
(författare)
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Genome-wide association study identifies multiple loci associated with bladder cancer risk
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 23:5, s. 1387-1398
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Tidskriftsartikel (refereegranskat)abstract
- andidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
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- Feola, Giuseppe, et al.
(författare)
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Researching farmer behaviour in climate change adaptation and sustainable agriculture: Lessons learned from five case studies
- 2015
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Ingår i: Journal of Rural Studies. - : Elsevier BV. - 0743-0167. ; 39, s. 74-84
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Tidskriftsartikel (refereegranskat)abstract
- Understanding farmer behaviour is needed for local agricultural systems to produce food sustainably while facing multiple pressures. We synthesize existing literature to identify three fundamental questions that correspond to three distinct areas of knowledge necessary to understand farmer behaviour: 1) decision-making model; 2) cross-scale and cross-level pressures; and 3) temporal dynamics. We use this framework to compare five interdisciplinary case studies of agricultural systems in distinct geographical contexts across the globe. We find that these three areas of knowledge are important to understanding farmer behaviour, and can be used to guide the interdisciplinary design and interpretation of studies in the future. Most importantly, we find that these three areas need to be addressed simultaneously in order to understand farmer behaviour. We also identify three methodological challenges hindering this understanding: the suitability of theoretical frameworks, the trade-offs among methods and the limited timeframe of typical research projects. We propose that a triangulation research strategy that makes use of mixed methods, or collaborations between researchers across mixed disciplines, can be used to successfully address all three areas simultaneously and show how this strategy has been achieved in the case studies. The framework facilitates interdisciplinary research on farmer behaviour by opening up spaces of structured dialogue on assumptions, research questions and methods employed in investigation. (C) 2015 Elsevier Ltd. All rights reserved.
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| 5. |
- Jiménez, Marcela, et al.
(författare)
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Assessing the historical adaptive cycles of an urban social-ecological system and its potential future resilience : the case of Xochimilco, Mexico City
- 2020
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Ingår i: Regional Environmental Change. - : Springer Science and Business Media LLC. - 1436-3798 .- 1436-378X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- As the bulk of the world’s population becomes urban, maintaining urban ecosystem services for environmental and social well-being in cities is crucial. According to resilience theory, maintaining such services requires for a complex adaptive systems perspective that helps in identifying key elements and dynamics behind cross-scale social-ecological interactions. In this context, the objective of this article is to use a resilience “lens” to problematize the imminent loss of an urban wetland using the adaptive cycle model as a heuristic tool. Our case study focuses on the Xochimilco wetland, located in the southern periphery of Mexico City. Xochimilco is characterized by the presence of a complex system of raised bed wetland agriculture (the chinampa system), which was established over 1000 years ago; currently, despite having a recognized cultural and environmental value, it is threatened by increasing urban sprawl, over-exploitation of the aquifer, and water contamination. By conducting a historical analysis of the Xochimilco social-ecological system, we assess how it has gone through phases of the adaptive cycle. As a result, we identify critical elements of the system’s historically maintained resilience and main drivers of system change. From such findings, we present some insights on the possibilities of maintaining the system’s resilience and guidance for future management strategies for the Xochimilco wetland. Lastly, we reflect on the scope and limitations of using a resilience-based approach and an adaptive cycle analysis for addressing urban sustainability problems, especially in cities in the Global South.
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