| 1. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 2. |
- 't Hart, Leen M., et al.
(författare)
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The CTRB1/2 Locus Affects Diabetes Susceptibility and Treatment via the Incretin Pathway
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:9, s. 3275-3281
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Tidskriftsartikel (refereegranskat)abstract
- The incretin hormone glucagon-like peptide 1 (GLP-1) promotes glucose homeostasis and enhances -cell function. GLP-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which inhibit the physiological inactivation of endogenous GLP-1, are used for the treatment of type 2 diabetes. Using the Metabochip, we identified three novel genetic loci with large effects (30-40%) on GLP-1-stimulated insulin secretion during hyperglycemic clamps in nondiabetic Caucasian individuals (TMEM114; CHST3 and CTRB1/2; n = 232; all P 8.8 x 10(-7)). rs7202877 near CTRB1/2, a known diabetes risk locus, also associated with an absolute 0.51 +/- 0.16% (5.6 +/- 1.7 mmol/mol) lower A1C response to DPP-4 inhibitor treatment in G-allele carriers, but there was no effect on GLP-1 RA treatment in type 2 diabetic patients (n = 527). Furthermore, in pancreatic tissue, we show that rs7202877 acts as expression quantitative trait locus for CTRB1 and CTRB2, encoding chymotrypsinogen, and increases fecal chymotrypsin activity in healthy carriers. Chymotrypsin is one of the most abundant digestive enzymes in the gut where it cleaves food proteins into smaller peptide fragments. Our data identify chymotrypsin in the regulation of the incretin pathway, development of diabetes, and response to DPP-4 inhibitor treatment.
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| 3. |
- Buytaert, Wouter, et al.
(författare)
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Citizen science in hydrology and water resources : opportunities for knowledge generation , ecosystem service management , and sustainable development
- 2014
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Ingår i: Frontiers in Earth Science. - : Frontiers Media SA. - 2296-6463. ; 2:October, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- The participation of the general public in the research design, data collection and interpretation process together with scientists is often referred to as citizen science. While citizen science itself has existed since the start of scientific practice, developments in sensing technology, data processing and visualization, and communication of ideas and results, are creating a wide range of new opportunities for public participation in scientific research. This paper reviews the state of citizen science in a hydrological context and explores the potential of citizen science to complement more traditional ways of scientific data collection and knowledge generation for hydrological sciences and water resources management. Although hydrological data collection often involves advanced technology, the advent of robust, cheap, and low-maintenance sensing equipment provides unprecedented opportunities for data collection in a citizen science context. These data have a significant potential to create new hydrological knowledge, especially in relation to the characterization of process heterogeneity, remote regions, and human impacts on the water cycle. However, the nature and quality of data collected in citizen science experiments is potentially very different from those of traditional monitoring networks. This poses challenges in terms of their processing, interpretation, and use, especially with regard to assimilation of traditional knowledge, the quantification of uncertainties, and their role in decision support. It also requires care in designing citizen science projects such that the generated data complement optimally other available knowledge. Lastly, using 4 case studies from remote mountain regions we reflect on the challenges and opportunities in the integration of hydrologically-oriented citizen science in water resources management, the role of scientific knowledge in the decision-making process, and the potential contestation to established community institutions posed by co-generation of new knowledge.
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| 4. |
- Sheate, W R, et al.
(författare)
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Spatial Representation and Specification of Ecosystem Services
- 2012
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Ingår i: Journal of Environmental Assessment Policy and Management. - 1464-3332 .- 1757-5605. ; 14:1, s. 1250001-1250036
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Tidskriftsartikel (refereegranskat)abstract
- The challenge for implementing an ecosystems approach to environmental decision-making processes, such as spatial planning, is to understand the range, nature and amount of ecosystem services currently provided and the potential for such service provision in the future. The ability to spatially represent ecosystems services is a critical element of the evidence base on which to make decisions about how physical space is used most effectively and sustainably, and the way people and activities are distributed at different spatial scales. This paper reports on the outcomes of a research project originally undertaken for the UK Department for the Environment, Food and Rural Affairs which developed a methodology for mapping ecosystem services using GIS and readily available, existing land use/land cover datasets. Critical components of the methodology, in order to determine which datasets are appropriate for which services, are network analysis and stakeholder engagement techniques, to define the relevant typology of ecosystem services and their relationship to land use/land cover types. The methodology was developed and tested successfully in the context of green grid (green infrastructure) networks in a major UK regeneration area, the Thames Gateway, to the east of London, and its potential use in impact assessment further explored through a number of case studies.
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| 5. |
- Voight, Benjamin F., et al.
(författare)
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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589
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Tidskriftsartikel (refereegranskat)abstract
- By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
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