| 1. |
-
- 2019
-
Journal article (peer-reviewed)
|
|
| 2. |
|
|
| 3. |
- Hudson, Thomas J., et al.
(author)
-
International network of cancer genome projects
- 2010
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
-
Journal article (peer-reviewed)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
|
|
| 4. |
- Gorski, Mathias, et al.
(author)
-
Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
-
In: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
-
Journal article (peer-reviewed)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
|
|
| 5. |
- Pattaro, Cristian, et al.
(author)
-
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)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.
|
|
| 6. |
- Gorski, Mathias, et al.
(author)
-
Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
-
In: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
-
Journal article (peer-reviewed)abstract
- Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
|
|
| 7. |
- Bonow, Johan M., et al.
(author)
-
A multi-disciplinary study of Phanerozoic landscape development in West Greenland
- 2007
-
In: Geological Survey of Denmark and Greenland Bulletin: Review of Survey activities 2006. - 1604-8156. ; :13, s. 33-36
-
Journal article (peer-reviewed)abstract
- The western margin of the Greenland craton has been muchless stable in the Phanerozoic than previously thought. Thisnew insight has come from close integration of independentdata sets: geomorphological analysis of large-scale landscapes,apatite fission track analysis (AFTA), onshore and offshorestratigraphy and analysis of onshore fault and fracture sys -tems. Each data set records specific and unique parts of theevent chronology and is equally important to establish a con-sistent model. A key area for understanding the Mesozoic-Cenozoic landscape evolution and into the present is theuplifted part of the Nuussuaq Basin, where remnants of pla-nation surfaces cut across the Cretaceous to Eocene sedimen-tary and volcanic rocks. Our integrated analysis concludedthat the West Greenland mountains were formed by lateNeogene tectonic uplift (Fig. 1) and also provided newinsight into early Phanerozoic development. To understandour model, we present the different methods and the resultsthat can be deduced from them.
|
|
| 8. |
- Bonow, Johan M., et al.
(author)
-
Cenozoic uplift of Nuussuaq and Disko, West Greenland : elevated erosion surfaces as uplift markers of a passive margin
- 2006
-
In: Geomorphology. - : Elsevier BV. - 0169-555X .- 1872-695X. ; 80:3-4, s. 325-337
-
Journal article (peer-reviewed)abstract
- Remnants of a high plateau have been identified on Nuussuaq and Disko, central West Greenland. We interpret the plateau as an erosion surface (the summit erosion surface) formed mainly by a fluvial system and graded close to its former base level and subsequently uplifted to its present elevation. It extends over 150 km east–west, being of low relative relief, broken along faults, tilted westwards in the west and eastwards in the east, and having a maximum elevation of ca. 2 km in central Nuussuaq and Disko. The summit erosion surface cuts across Precambrian basement rocks and Paleocene–Eocene lavas, constraining its age to being substantially younger than the last rift event in the Nuussuaq Basin, which took place during the late Maastrichtian and Danian. The geological record shows that the Nuussuaq Basin was subjected to subsidence of several kilometres during Paleocene–Eocene volcanism and was transgressed by the sea later during the Eocene. By comparing with results from apatite fission track analysis and vitrinite reflectance maturity data, it is suggested that formation of the erosion surface was probably triggered by an uplift and erosion event starting between 40 and 30 Ma. Surface formation was completed prior to an uplift event that started between 11 and 10 Ma and caused valley incision. This generation of valleys graded to the new base level and formed a lower erosion surface, at most 1 km below the summit erosion surface, thus indicating the magnitude of its uplift. Formation of this generation of valleys was interrupted by a third uplift event also with a magnitude of 1 km that lifted the landscape to near its present position. Correlation with the fission-track record suggests that this uplift event started between 7 and 2 Ma. Uplift must have been caused initially by tectonism. Isostatic compensation due to erosion and loading and unloading of ice sheets has added to the magnitude of uplift but have not significantly altered the configuration of the surface. It is concluded that the elevations of palaeosurfaces (surfaces not in accordance with present climate or tectonic conditions) on West Greenland's passive margin can be used to define the magnitude and lateral variations of Neogene uplift events. The striking similarity between the landforms in West Greenland and those on many other passive margins is also noted.
|
|
| 9. |
- Bonow, Johan M., et al.
(author)
-
Elevated erosion surfaces in central West Greenland and southern Norway: their significance in integrated studies of passive margin development
- 2007
-
In: Norwegian Journal of Geology. - 0029-196X. ; 87, s. 197-206
-
Journal article (peer-reviewed)abstract
- Elevated erosion surfaces were used as an independant data set in an integrated study of the landscape development in central West Greenland. The study resulted in a time-constrained model describing multiple episodes of post-rift uplift, erosion and burial on a passive margin. The model is based on full integration of three data sets: analysis of large-scale landforms, apatite fission track analysis (AFTA) of samples from outcrops and deep boreholes, and the geological record. These data are equally important as they record specific an unique parts of the landscape history. The relative chronology obtained from the landform record is constrained by geology, which gives the maximum age of an erosin surface, and AFTA that records the cooling history of the subsurface rock. This combined approach validates the interpretation of erosion surface as having been goverened by different base levels in the past, and shows that erosion surfaces can be used to reconstruct tectonic events. Geomorphological key observations for the landscapes of southern Norway are presented and the similarities with landscapes in central West Greenland emphasised, especially the elevated plateaux and the Mesozoic etch surfaces. This similarity suggests that it may be possible to construct a time-constrained model for the landscape development of southern Norway based on our West Greenland approach.
|
|
| 10. |
- Chalmers, James, et al.
(author)
-
Sixty years of second language aptitude research : A systematic quantitative literature review
- 2021
-
In: Language and Linguistics Compass. - : John Wiley & Sons. - 1749-818X. ; 15:11
-
Research review (peer-reviewed)abstract
- Second language (L2) aptitude has been broadly defined as the rate and ease of initially acquiring a second language. Historically, L2 aptitude has been understood as a stable trait that predetermined L2 achievement, regardless of individual learners’ efforts to acquire an L2. This traditional view of L2 aptitude as fixed and stable has led to it being a relatively neglected area of research within second language acquisition (SLA) studies. The little research that was in fact conducted was diagnostic in nature, and mostly used tests such as the Modern Language Aptitude Test (MLAT) to select potentially gifted L2 learners. Given that six decades have passed since the publication of the MLAT, now is a good time to revisit the literature and investigate whether L2 aptitude continues to be viewed as an individual difference of little interest to SLA research. While summative literature reviews of L2 aptitude research have been written, few systematic reviews exist. This article conducts a systematic quantitative literature review (SQLR) to provide a principled, comprehensive and reproducible synthesis of research into L2 aptitude published over the last 60 years (1959–2019). In this SQLR, close to one hundred journal articles and PhD dissertations were examined to discern generalisations and limitations in the field. This SQLR identifies a shift in the rationale for L2 aptitude testing, in which a diagnostic focus has been replaced by an explanatory perspective. Furthermore, our article points to a renewed interest in L2 aptitude research, which has come to be characterised by a more nuanced and sophisticated understanding of the concept and its components.
|
|
