| 1. |
- Koettgen, Anna, et al.
(författare)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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| 2. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 3. |
- Alonso Aller, Elisa, et al.
(författare)
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Temporal variability of a protected multispecific tropical seagrass meadow in response to environmental change
- 2019
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Ingår i: Environmental Monitoring and Assessment. - : Springer Science and Business Media LLC. - 0167-6369 .- 1573-2959. ; 191
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Tidskriftsartikel (refereegranskat)abstract
- In a changing environment, there is an increasing interest to monitor ecosystems to understand their responses to environmental change. Seagrass meadows are highly important ecosystems that are under constant pressure from human activities and climate impacts, with marked declines observed worldwide. Despite increasing efforts, monitoring of multispecific tropical seagrass meadows is scarce, particularly in low-income regions. Based on data from a monitoring programme in a marine protected area in Zanzibar (Tanzania), we assessed temporal changes in seagrass cover and species composition during a 10-year period in relation to local variability in environmental variables. We observed a strong, gradual decline in seagrass cover and changes in species composition, followed by a period of recovery. However, the timing and length of these temporal patterns varied in space (between transects). Multiple environmental variables—cloud cover, temperature, storm occurrence, sunspot activity, and tidal amplitude and height—influenced seagrass cover, although only to a minor extent, suggesting that the monitored seagrass meadow may be influenced by other unmeasured factors (e.g. water currents and sediment movement). Our results show that seagrass meadows can be highly dynamic at small (10–50 m) spatial scales, even in the absence of major local anthropogenic impacts. Our findings suggest that high-resolution monitoring programmes can be highly valuable for the detection of temporal changes in multispecific seagrass meadows; however, to understand the causes of change, there is a need of long-term (> 10 years) data series that include direct measurements of environmental variables and extreme events.
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