| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Ades, M., et al.
(författare)
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Global Climate : in State of the climate in 2019
- 2020
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Ades, M., et al.
(författare)
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GLOBAL CLIMATE
- 2020
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Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Arndt, D. S., et al.
(författare)
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State of the Climate in 2016
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Tidskriftsartikel (refereegranskat)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 5. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 6. |
- Chasman, Daniel I., et al.
(författare)
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Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343
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Tidskriftsartikel (refereegranskat)abstract
- In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
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| 7. |
- Holmfeldt, Linda, et al.
(författare)
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The genomic landscape of hypodiploid acute lymphoblastic leukemia
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:3, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
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| 8. |
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| 9. |
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| 10. |
- Issa, Issa E
(författare)
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Sedimentological and Hydrological Investigation of Mosul Dam Reservoir
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Reservoir sedimentation is the main problem that directly affects the performance of dams due to the reduction in the storage capacity of their reservoirs. Monitoring the storage capacity of reservoirs is an important issue for the planners, designers and operators of the dams. Iraq mainly depends on the rivers Tigris and Euphrates for its water resources. Until the 1970s, Iraq was regarded as a rich country with regard to its water resources, due to the presence of the Tigris and Euphrates rivers. Recently, its water resources have decreased significantly due to an increased water demand and global climate changes. In view of this situation, it became necessary to know about Iraq’s water resource trends to adopt prudent water resource management strategies. Among these strategies is the assessment of the sedimentation rates in its reservoirs to determine their actual storage capacities and reduction rates of storage capacity through time. Mosul Dam Reservoir (MDR) is the biggest and one of the most important strategic projects in Iraq. It is a multipurpose project constructed to store water and to handle flood control and hydropower generation but the main purpose was to provide water for three irrigation projects that cover 2,500 km2 of agricultural areas. The dam is located on the River Tigris in northern Iraq, 60 km north-west of the city of Mosul. The project was designed to store 11.11 km3 with water surface area of about 380 km2 at the maximum operation level 330 m a.s.l. It is noteworthy to mention that MDR has operated since 1986, and no detailed studies have been carried out to determine the sedimentation characteristics in its reservoir since that time. In the present work, the storage capacity, sedimentation rates, area-storage capacity (ASC) curves, sediment nature and their grain size distribution and bottom morphology of its reservoir were studied. Direct and indirect methods were used to achieve these goals. In the direct methods, two topographic maps for MDR’s area were established in a triangular irregular network (TIN) format using Arc/GIS software. One of them before dam construction from pre-construction topographic map scale 1:50000 and other from bathymetric survey that was conducted in 2011. These maps were used; to calculate the volume of deposited sediment, to develop and evaluate ASC curves, to determine the bed morphology and to estimate the useful life of MDR. The results of the two surveys indicated that 1.143 km3 of sediment were deposited in MDR during the 25 years of its operation. This implies that the reduction in its original storage capacity was 10.29% with an annual reduction rate of 0.441% which is less than the sedimentation rates in the worldwide and Middle East. Furthermore, the results showed that 0.563 km3 and 0.58 km3 of sediment were deposited in live storage and dead storage zones respectively. This indicates that the live and dead storage zones lost 6.9% and 19.66% of their storage capacity till 2011 respectively. According to these results, MDR’s useful life will be about 127 years or 121.5 years based on the depletion of its dead storage or 50% of its maximum storage capacity respectively. Likewise, the survey suggested new ASC curves for MDR. Comparison of the two TIN maps showed most of the sediment was deposited in the upper part of MDR, where the River Tigris enters MDR and it gradually reduced towards the dam site. There were erosion areas within the reservoir and mainly close to the dam body which might be due to dissolving the gypsum.In addition, fifty six sediment samples were collected from the bottom of its reservoir to study the nature of sediment deposited using the Van-Veen grab sampler. The samples were covering most of the reservoir area. The results revealed that the sediments were comprised of gravel, sand, silt and clay in the ratios 3.8%, 15%, 55.5% and 25.7% respectively. The distribution of these sediments indicates that the silt portion represents the highest or 77% of the bottom sediment of this reservoir followed by clay 13.5% and then sand with gravel 9.5%. However, sand percentages are the highest in the northern zone of the reservoir where the River Tigris enters the reservoir and decrease gradually towards the dam site. In the meantime, silt percentage decreases towards the dam site whilst the finer fraction (i.e. clay) increases. The sediment is poorly sorted, nearly symmetrical in skewness and leptokurtic, very leptokurtic, to mesocratic.Indirect approaches using several empirical and semi-empirical techniques to determine sedimentation characteristics in MDR were used. Three empirical approaches based on the particle grain size of the sediment deposited showed that MDR’s useful life ranged from 122.5 to 132 years. Six different empirical methods to determine the sediment trap efficiency (TE) of MDR were adopted. These methods were based on the residence time principle (water retention time). The methods were used to determine monthly TE and long-term TE for MDR for the period 1986 to 2011. The TE results with sediment entering MDR were used to calculate the amount of sediment deposited during its operational period. The comparison of the results with the bathymetric survey showed that all techniques gave good agreement, especially those depending on monthly TE, but the method that was proposed for large dams gave a more accurate result with 0.350% percentage error. To find out the sediment deposited depth at the Mosul dam site and to establish and predict changes in its ASC curves, four empirical and semi-empirical techniques were used for MDR. The results obtained were evaluated using the bathymetric survey data. The comparison of the results for establishing the ASC curves showed that one method agreed with bathymetric results whilst two methods gave good results for the sedimentation depth at the dam site. Furthermore, three of these methods were modified to predict the future changes in the ASC curves with sedimentation, based on the data from 11 reservoirs in the USA. The modified approaches were applied to MDR to predict the future ASC curves for 50, 75, 100 and 125 years. The curves predicted by these methods demonstrated compliance with the method adopted by the U.S. Bureau of Reclamation ‘area reduction method’. Finally, the indirect approaches can help decision makers, planners and designers, to monitor sedimentation characteristics and to implement prudent strategies for management of MDR in the future and to know the most suitable technique to adopt for MDR in the future.
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| 11. |
- Issa, Issa E.
(författare)
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Siltation and sedimentation problem in Mosul reservoir dam
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Iraq depends on the Rivers Tigris and Euphrates for its water resources. Recently the flow of these rivers decreased drastically. In view of this situation the true storage capacity of the dams are to be evaluated to ensure prudent water resources management strategies. In this research, the biggest hydraulic structure in Iraq, Mosul Dam Reservoir, was studied to evaluate its present storage capacity.Mosul dam reservoir is located on the River Tigris in the north of Iraq, 60 km north-west Mosul city. The dam is a multipurpose project for irrigation, flood control and hydropower generation. The storage capacity of its reservoir is 11.11×109 m3 and water surface area is 380 km2 at the maximum operation level 330 m.a.s.l. The dam was operated on July 24th, 1986 and no survey had been conducted to determine its storage capacity since that time. A pre-construction topographic map for the studied area scale 1: 50000 dated 1983 was converted to a triangular irregular network (TIN) format using “Arc/GIS software version 9.3”. The TIN was used to establish the stage-area and stage-storage capacity curves before dam construction. The resultant curves were compared with the adopted operational curves. The results of this comparison showed that the percentage difference was 4.0% and 7.7% for stage-storage capacity and stage-water surface area curves respectively.Mosul reservoir was surveyed to find out the reduction in its storage capacity and to develop new operational curves. The survey was performed over 12 days from May 15th to June 3rd, 2011 using to “Echo sounder sonar viewer type Sea Charter 480DF” linked to a “Real-Time Kinematic Global Positioning System (RTK-GPS)”. The bathymetric survey results indicated that the reduction in the storage capacity of the reservoir due to sediment deposition during the operating period was 1.143×109 m3. This represents 14.73% of the total storage capacity and the reduction in the live storage and dead storage was 11.8% and 19.62% respectively. Likewise, the survey suggested new operational curves for Mosul dam reservoir. The survey showed that most of the sedimentation was in the upper zone of the reservoir and gradually decreased towards the dam.
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| 12. |
- Kaufman, Darrell, et al.
(författare)
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A global database of Holocene paleotemperature records
- 2020
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive database of paleoclimate records is needed to place recent warming into the longer-term context of natural climate variability. We present a global compilation of quality-controlled, published, temperature-sensitive proxy records extending back 12,000 years through the Holocene. Data were compiled from 679 sites where time series cover at least 4000 years, are resolved at sub-millennial scale (median spacing of 400 years or finer) and have at least one age control point every 3000 years, with cut-off values slackened in data-sparse regions. The data derive from lake sediment (51%), marine sediment (31%), peat (11%), glacier ice (3%), and other natural archives. The database contains 1319 records, including 157 from the Southern Hemisphere. The multi-proxy database comprises paleotemperature time series based on ecological assemblages, as well as biophysical and geochemical indicators that reflect mean annual or seasonal temperatures, as encoded in the database. This database can be used to reconstruct the spatiotemporal evolution of Holocene temperature at global to regional scales, and is publicly available in Linked Paleo Data (LiPD) format.
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| 13. |
- Kennedy, Ken, et al.
(författare)
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Toward a Framework for Preparing and Executing Adaptive Grid Programs
- 2002
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Konferensbidrag (refereegranskat)abstract
- This paper describes the program execution framework being developed by the Grid Application Development Software (GrADS) Project . The goal of this framework is to provide good resource allocation for Grid applications and to support adaptive reallocation if performance degrades because of changes in the availability of Grid resources. At the heart of this strategy is the notion of a configurable object program, which contains, in addition to application code, strategies for mapping the application to different collections of resources and a resource selection model that provides an estimate of the performance of the application on a specific collection of Grid resources. This model must be accurate enough to distinguish collections of resources that will deliver good performance from those that will not. The GrADS execution framework also provides a contract monitoring mechanism for interrupting and remapping an application execution when performance falls below acceptable levels.
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| 14. |
- Meyer, Peter A., et al.
(författare)
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Data publication with the structural biology data grid supports live analysis
- 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
- Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data. sbgrid. org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis.
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| 15. |
- Parsa, Afshin, et al.
(författare)
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Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
- 2013
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 24:12, s. 2105-2117
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Tidskriftsartikel (refereegranskat)abstract
- Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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| 16. |
- 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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| 17. |
- Pattaro, Cristian, et al.
(författare)
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Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002584-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
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| 18. |
- Walker, Steven M, et al.
(författare)
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Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:4, s. 509-518
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.OBJECTIVE: To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy.DESIGN, SETTING, AND PARTICIPANTS: Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis.RESULTS AND LIMITATIONS: A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation.CONCLUSIONS: The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential.PATIENT SUMMARY: The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.
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