| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- Berndt, Christian, et al.
(författare)
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Northeast Atlantic breakup volcanism and consequences for Paleogene climate change - MagellanPlus Workshop report
- 2019
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Ingår i: Scientific Drilling. - : Copernicus GmbH. - 1816-8957 .- 1816-3459. ; 26, s. 69-85
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Tidskriftsartikel (refereegranskat)abstract
- The northeast Atlantic encompasses archetypal examples of volcanic rifted margins. Twenty-five years after the last ODP (Ocean Drilling Program) leg on these volcanic margins, the reasons for excess melting are still disputed with at least three competing hypotheses being discussed. We are proposing a new drilling campaign that will constrain the timing, rates of volcanism, and vertical movements of rifted margins. This will allow us to parameterise geodynamic models that can distinguish between the hypotheses. Furthermore, the drilling-derived data will help us to understand the role of breakup magmatism as a potential driver for the Palaeocene-Eocene thermal maximum (PETM) and its influence on the oceanographic circulation in the earliest phase of the northeast Atlantic Ocean formation. Tackling these questions with a new drilling campaign in the northeast Atlantic region will advance our understanding of the long-term interactions between tectonics, volcanism, oceanography, and climate and the functioning of subpolar northern ecosystems and climate during intervals of extreme warmth.
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| 4. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 5. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 6. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 7. |
- Robinson, Adam H., et al.
(författare)
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Multiscale characterisation of chimneys/pipes : Fluid escape structures within sedimentary basins
- 2021
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Ingår i: International Journal of Greenhouse Gas Control. - : Elsevier BV. - 1750-5836 .- 1878-0148. ; 106
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Tidskriftsartikel (refereegranskat)abstract
- Evaluation of seismic reflection data has identified the presence of fluid escape structures cross-cutting overburden stratigraphy within sedimentary basins globally. Seismically-imaged chimneys/pipes are considered to be possible pathways for fluid flow, which may hydraulically connect deeper strata to the seabed. The properties of fluid migration pathways through the overburden must be constrained to enable secure, long-term subsurface carbon dioxide (CO2) storage. We have investigated a site of natural active fluid escape in the North Sea, the Scanner pockmark complex, to determine the physical characteristics of focused fluid conduits, and how they control fluid flow. Here we show that a multi-scale, multi-disciplinary experimental approach is required for complete characterisation of fluid escape structures. Geophysical techniques are necessary to resolve fracture geometry and subsurface structure (e.g., multi-frequency seismics) and physical parameters of sediments (e.g., controlled source electromagnetics) across a wide range of length scales (m to km). At smaller (mm to cm) scales, sediment cores were sampled directly and their physical and chemical properties assessed using laboratory-based methods. Numerical modelling approaches bridge the resolution gap, though their validity is dependent on calibration and constraint from field and laboratory experimental data. Further, time-lapse seismic and acoustic methods capable of resolving temporal changes are key for determining fluid flux. Future optimisation of experiment resource use may be facilitated by the installation of permanent seabed infrastructure, and replacement of manual data processing with automated workflows. This study can be used to inform measurement, monitoring and verification workflows that will assist policymaking, regulation, and best practice for CO2 subsurface storage operations.
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| 8. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 9. |
- 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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| 10. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 11. |
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| 12. |
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| 13. |
- Böttner, Christoph, et al.
(författare)
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Pockmarks in the Witch Ground Basin, Central North Sea
- 2019
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Ingår i: Geochemistry Geophysics Geosystems. - 1525-2027. ; 20:4, s. 1698-1719
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Tidskriftsartikel (refereegranskat)abstract
- Marine sediments host large amounts of methane (CH4), which is a potent greenhouse gas. Quantitative estimates for methane release from marine sediments are scarce, and a poorly constrained temporal variability leads to large uncertainties in methane emission scenarios. Here, we use 2-D and 3-D seismic reflection, multibeam bathymetric, geochemical, and sedimentological data to (I) map and describe pockmarks in the Witch Ground Basin (central North Sea), (II) characterize associated sedimentological and fluid migration structures, and (III) analyze the related methane release. More than 1,500 pockmarks of two distinct morphological classes spread over an area of 225 km(2). The two classes form independently from another and are corresponding to at least two different sources of fluids. Class 1 pockmarks are large in size (> 6 m deep, > 250 m long, and > 75 m wide), show active venting, and are located above vertical fluid conduits that hydraulically connect the seafloor with deep methane sources. Class 2 pockmarks, which comprise 99.5% of all pockmarks, are smaller (0.9-3.1 m deep, 26-140 m long, and 14-57 m wide) and are limited to the soft, fine-grained sediments of the Witch Ground Formation and possibly sourced by compaction-related dewatering. Buried pockmarks within the Witch Ground Formation document distinct phases of pockmark formation, likely triggered by external forces related to environmental changes after deglaciation. Thus, greenhouse gas emissions from pockmark fields cannot be based on pockmark numbers and present-day fluxes but require an analysis of the pockmark forming processes through geological time. Plain Language Summary Marine sediments host large amounts of methane (CH4), which is a potent greenhouse gas. The amount of methane released into the atmosphere is, however, largely unknown making it difficult to implement this methane source in climate models. Here we use geophysical, geochemical, and sedimentological data to map the distribution of fluid escape structures in the central North Sea. More than 1,500 pockmarks, which are circular to semicircular depressions of the seafloor, indicate fluid flow from the subsurface. There are two distinct morphological classes of pockmarks corresponding to at least two different fluid sources. Class 1 pockmarks are large, show active venting, and are located above vertical fluid conduits in the subsurface, which feed fluids from deeper strata. Class 2 pockmarks, which comprise 99.5% of all pockmarks, are smaller and limited to the soft sediments directly below the seafloor. Older pockmarks in the subsurface document distinct phases of pockmark formation, likely triggered by external forces after the retreat of ice in the North Sea. The amount of methane released from natural geological sources based on pockmark numbers may be wrong as these do not take into account the origin and composition of released fluids.
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| 14. |
- Böttner, Christoph, et al.
(författare)
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Pockmarks in the Witch Ground Basin, Central North Sea
- 2019
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Ingår i: Geochemistry Geophysics Geosystems. - : American Geophysical Union (AGU). - 1525-2027. ; 20:4, s. 1698-1719
-
Tidskriftsartikel (refereegranskat)abstract
- Marine sediments host large amounts of methane (CH4), which is a potent greenhouse gas. Quantitative estimates for methane release from marine sediments are scarce, and a poorly constrained temporal variability leads to large uncertainties in methane emission scenarios. Here, we use 2-D and 3-D seismic reflection, multibeam bathymetric, geochemical, and sedimentological data to (I) map and describe pockmarks in the Witch Ground Basin (central North Sea), (II) characterize associated sedimentological and fluid migration structures, and (III) analyze the related methane release. More than 1,500 pockmarks of two distinct morphological classes spread over an area of 225 km2. The two classes form independently from another and are corresponding to at least two different sources of fluids. Class 1 pockmarks are large in size (>6 m deep, >250 m long, and >75 m wide), show active venting, and are located above vertical fluid conduits that hydraulically connect the seafloor with deep methane sources. Class 2 pockmarks, which comprise 99.5% of all pockmarks, are smaller (0.9–3.1 m deep, 26–140 m long, and 14–57 m wide) and are limited to the soft, fine-grained sediments of the Witch Ground Formation and possibly sourced by compaction-related dewatering. Buried pockmarks within the Witch Ground Formation document distinct phases of pockmark formation, likely triggered by external forces related to environmental changes after deglaciation. Thus, greenhouse gas emissions from pockmark fields cannot be based on pockmark numbers and present-day fluxes but require an analysis of the pockmark forming processes through geological time.
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| 15. |
- Dalerum, Fredrik, et al.
(författare)
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The influence of distance to perennial surface water on ant communities in Mopane woodlands, northern Botswana
- 2019
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 9:1, s. 154-165
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Tidskriftsartikel (refereegranskat)abstract
- Studies of biodiversity along environmental gradients provide information on how ecological communities change in response to biotic and abiotic factors. For instance, distance to water is associated with several factors that shape the structure and the functioning of ecosystems at a range of spatial scales. We investigated the influence of distance to a perennial water source on ant communities in a semi-arid savanna in northern Botswana. Ant abundance, taxonomic richness, and both alpha and beta diversity were generally higher during the wet than the dry season. However, there were strong seasonal influences on the effects of distance to water, with more pronounced effects during the wet season. While both abundance and beta diversity declined with increasing distances to water during the wet season, there was a contrasting increase in alpha diversity. There was no major effect of distance to water on taxonomic richness during either season. Beta diversity was as high across as along gradients, and we found support for modular rather than nested community structures along gradients. Our study demonstrated that small-scale gradients in distance to water can influence several aspects of ant communities in semi-arid savannas. However, our results also point to strong effects of small-scale environmental variation, for instance associated with vegetation characteristics, soil properties, and plant community structure that are not directly linked to water access.
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| 16. |
- De Gregorio, Julia
(författare)
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Trading animal genetics : On the “marketization” of bovine genetics in the dairy industry
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis studies the workings of markets in the specific context of the international trade in bovine genetics in the dairy industry and with a particular focus on the Global North. It draws upon the examples of trade in breeding stock – cows – at auction sales and trade in bovine semen.Inspired by the work of economic sociologist and actor network theorist Michel Callon on “marketization”, the thesis uses a performative approach to the market economy. Hence it does not address animals and their live body parts as simply being commodities. Rather it looks at processes that “make” them become commodities. Engaging with the question of how animals and their live body parts are turned into commodities, it is primarily concerned with valuation and bio-securitization processes and with the role of the animals themselves in the commodification process. Examining mechanisms that allow for the workings of markets in spite of not only pre-existing obstacles but of differences, resistances and instabilities – potential limitations – arising in the process of trading itself, the thesis focuses on the iterative character of markets.Based on findings derived from three empirical case studies, it shows how various forms of distinction are created in the marketization process of dairy genetics, and it demonstrates how these distinctions allow for trade. But the thesis also reveals mechanisms of distraction, suggesting that if markets operate on the basis of various forms of distinction, they do so simultaneously via mechanisms that distract us from the very distinctions created. It highlights the role of the human-animal divide in such processes.The thesis is based upon ethnographic and interview-based fieldwork mainly conducted in Germany and in New Zealand. Triangulating between work on “marketization”, the political economies of nature and nonhuman “lively commodities” in economic geography, and also on biosecurity, it seeks to make a contribution to these geographical literatures.
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| 17. |
- Elger, Judith, et al.
(författare)
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Core‐log‐seismic integration in metamorphic rocks and its implication for the regional geology : A case study for the ICDP drilling project COSC‐1, Sweden
- 2021
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Ingår i: Geochemistry Geophysics Geosystems. - : American Geophysical Union (AGU). - 1525-2027. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- Continental collision causes deformation in the crust along shear zones. However, the physical and chemical conditions at which these zones operate and the deformation processes that enable up to hundreds of km of tectonic transport are still unclear because of the depth at which they occur and the challenges in imaging them. Ancient exhumed collision zones allow us to investigate these processes much better, for example at the COSC‐1 borehole in the central Scandinavian Caledonides. This study combines data from the COSC‐1 borehole with different seismic measurements to provide constraints on the spatial lithological and textural configuration of the Seve Nappe Complex. This is one of the few studies that shows that core‐log‐seismic integration in metamorphic rocks allows to identify the spatial distribution of major lithological units. Especially gamma ray logs in combination with density data are powerful tools to distinguish between mafic and felsic lithologies in log‐core correlation. Our results indicate that reflections along the borehole are primarily caused by compositional rather than textural changes. Reflections in the Seve Nappe Complex are not as distinct as in greater depths but continuous and several of them can be linked to magmatic intrusions, which have been metamorphically overprinted. Their setting indicates that the Seve Nappe Complex consists of the remnants of a volcanic continental margin. Our results suggest that ductile‐deformed middle crustal reflectivity is primarily a function of pre‐orogenic lithological variations which has to be considered when deciphering mountain building processes.Plain Language SummaryAreas where continents collide experience different kind of deformation. However, these processes and the conditions at which they take place are difficult to study because of the great depth at which they occur. Former collision zones that are closer to the surface these days allow the investigation of these processes much better, for example at the COSC‐1 borehole in the central Scandinavian Caledonides. The challenge remains to image the remnant of these processes in high detail but at the same time over a large area. This study combines data from the COSC‐1 borehole with different geophysical measurements to better understand the lithology and structure of the Seve Nappe Complex. We show that the combination of these data allows us to distinguish between rocks from mafic and sedimentary origin. Our results indicate that the geophysical data along the borehole image the change of the composition of the rocks which probably originates from magmatic intrusions and have been overprinted by geological processes, rather than from fracture zones.
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| 18. |
- Gernigon, Laurent, et al.
(författare)
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Understanding volcanic margin evolution through the lens of Norway's youngest granite
- 2024
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Ingår i: Terra Nova. - : John Wiley & Sons. - 0954-4879 .- 1365-3121. ; 36:4, s. 250-257
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Tidskriftsartikel (refereegranskat)abstract
- Three boreholes drilled during the International Ocean Discovery Program (IODP) Expedition 396 have yielded unexpected findings of altered granitic rocks covered by basalt flows, interbedded sediments and glacial mud near the continent-ocean transition of the mid-Norwegian margin. U-Pb and K-Ar geochronological analyses were conducted on both protolithic and authigenically formed K-bearing minerals to determine the age of granite crystallisation and subsequent alteration episodes. The granite's crystallisation age based on 104 zircons is 56.3 ± 0.2 Ma, and subsequent exhumation along with alteration/weathering events took place between 54.7 ± 1 and 37.1 ± 1 Ma. This intrusion represents the youngest granite discovered in Norway and intruded at an extremely shallow crustal level before a rapid rift-to-drift transition. The shallow emplacement of granitic rock and its fast exhumation before and during the onset of volcanism holds significant implications for the syn- and post-breakup tectonic evolution of volcanic margins.
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| 19. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 20. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 21. |
- Kaestner, Felix, et al.
(författare)
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Anisotropic velocity models for (3-D) seismic imaging of the Lower Seve Nappe in Jamtland, Sweden
- 2022
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Ingår i: Geophysical Journal International. - : Oxford University Press (OUP). - 0956-540X .- 1365-246X. ; 228:1, s. 66-77
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Tidskriftsartikel (refereegranskat)abstract
- Strong anisotropy of seismic velocity in the Earth's crust poses serious challenges for seismic imaging. Where in situ seismic properties are not available, the anisotropy can be determined from velocity analysis of surface and borehole seismic profiles. This is well established for dense, long-offset reflection seismic data. However, it is unknown how applicable this approach is for sparse seismic reflection data with low fold and short offsets in anisotropic metamorphic rocks. Here, we show that anisotropy parameters can be determined from a sparse 3-D data set at the COSC-1 borehole site in the Swedish Caledonides and that the results agree well with the seismic anisotropy parameters determined from seismic laboratory measurements on core samples. Applying these anisotropy parameters during 3-D seismic imaging improves the seismic image of the high-amplitude reflections especially in the vicinity of the lower part of the borehole. Strong reflections in the resulting seismic data show good correlation with the borehole-derived lithology. Our results aid the interpretation and extrapolation of the seismic stratigraphy of the Lower Seve Nappe in Jamtland and other parts in the Caledonides.
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| 22. |
- Karstens, Jens, et al.
(författare)
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Formation of the Figge Maar Seafloor Crater During the 1964 B1 Blowout in the German North Sea
- 2022
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Ingår i: Earth Science, Systems and Society. - : Frontiers Media SA. - 2634-730X. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- In 1964, exploration drilling in the German Sector of the North Sea hit a gas pocket at ∼2900 m depth below the seafloor and triggered a blowout, which formed a 550 m-wide and up to 38 m deep seafloor crater now known as Figge Maar. Although seafloor craters formed by fluid flow are very common structures, little is known about their formation dynamics. Here, we present 2D reflection seismic, sediment echosounder, and multibeam echosounder data from three geoscientific surveys of the Figge Maar blowout crater, which are used to reconstruct its formation. Reflection seismic data support a scenario in which overpressured gas ascended first through the lower part of the borehole and then migrated along steeply inclined strata and faults towards the seafloor. The focused discharge of gas at the seafloor removed up to 4.8 Mt of sediments in the following weeks of vigorous venting. Eyewitness accounts document that the initial phase of crater formation was characterized by the eruptive expulsion of fluids and sediments cutting deep into the substrate. This was followed by a prolonged phase of sediment fluidization and redistribution widening the crater. After fluid discharge ceased, the Figge Maar acted as a sediment trap reducing the crater depth to ∼12 m relative to the surrounding seafloor in 2018, which corresponds to an average sedimentation rate of ∼22,000 m3/yr between 1995 and 2018. Hydroacoustic and geochemical data indicate that the Figge Maar nowadays emits primarily biogenic methane, predominantly during low tide. The formation of Figge Maar illustrates hazards related to the formation of secondary fluid pathways, which can bypass safety measures at the wellhead and are thus difficult to control.
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| 23. |
- Lettre, Guillaume, et al.
(författare)
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Identification of ten loci associated with height highlights new biological pathways in human growth
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 584-591
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Tidskriftsartikel (refereegranskat)abstract
- Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet- undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in 410,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for similar to 2% of the population variation in height. Individuals with <= 8 height-increasing alleles and >= 16 height-increasing alleles differ in height by similar to 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait.
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| 24. |
- Loos, Ruth J. F., et al.
(författare)
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Common variants near MC4R are associated with fat mass, weight and risk of obesity
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:6, s. 768-775
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Tidskriftsartikel (refereegranskat)abstract
- To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.
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| 25. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 26. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 27. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 28. |
- Vardelle, Armelle, et al.
(författare)
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Erratum to The 2016 Thermal Spray Roadmap
- 2017
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Ingår i: Journal of thermal spray technology (Print). - : Springer Science and Business Media LLC. - 1059-9630 .- 1544-1016. ; 26:5, s. 985-986
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Tidskriftsartikel (refereegranskat)
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| 29. |
- Vardelle, Armelle, et al.
(författare)
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The 2016 Thermal Spray Roadmap
- 2016
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Ingår i: Journal of thermal spray technology (Print). - : Springer Science and Business Media LLC. - 1059-9630 .- 1544-1016. ; 25:8, s. 1376-1440
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Tidskriftsartikel (refereegranskat)abstract
- Considerable progress has been made over the last decades in thermal spray technologies, practices and applications. However, like other technologies, they have to continuously evolve to meet new problems and market requirements. This article aims to identify the current challenges limiting the evolution of these technologies and to propose research directions and priorities to meet these challenges. It was prepared on the basis of a collection of short articles written by experts in thermal spray who were asked to present a snapshot of the current state of their specific field, give their views on current challenges faced by the field and provide some guidance as to the R&D required to meet these challenges. The article is divided in three sections that deal with the emerging thermal spray processes, coating properties and function, and biomedical, electronic, aerospace and energy generation applications. © 2016, ASM International.
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| 30. |
- Willer, Cristen J., et al.
(författare)
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Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
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| 31. |
- Wolpin, Brian M., et al.
(författare)
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Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:9, s. 994-
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Tidskriftsartikel (refereegranskat)abstract
- We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 x 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 x 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 x 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 x 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 x 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 x 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.
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| 32. |
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| 33. |
- Wu, Lang, et al.
(författare)
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Identification of Novel Susceptibility Loci and Genes for Prostate Cancer Risk : A Transcriptome-Wide Association Study in over 140,000 European Descendants
- 2019
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:13, s. 3192-3204
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association study-identified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many of these identified associations remain unknown. To discover novel prostate cancer genetic loci and possible causal genes at previously identified risk loci, we performed a transcriptome-wide association study in 79,194 cases and 61,112 controls of European ancestry. Using data from the Genotype-Tissue Expression Project, we established genetic models to predict gene expression across the transcriptome for both prostate models and cross-tissue models and evaluated model performance using two independent datasets. We identified significant associations for 137 genes at P < 2.61 x 10(-6), a Bonferroni-corrected threshold, including nine genes that remained significant at P < 2.61 x 10(-6) after adjusting for all known prostate cancer risk variants in nearby regions. Of the 128 remaining associated genes, 94 have not yet been reported as potential target genes at known loci. We silenced 14 genes and many showed a consistent effect on viability and colony-forming efficiency in three cell lines. Our study provides substantial new information to advance our understanding of prostate cancer genetics and biology. Significance: This study identifies novel prostate cancer genetic loci and possible causal genes, advancing our understanding of the molecular mechanisms that drive prostate cancer.
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| 34. |
- Yang, Jian, et al.
(författare)
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FTO genotype is associated with phenotypic variability of body mass index
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 490:7419, s. 267-272
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using similar to 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)(5-7), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of similar to 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation(9,10). Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
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| 35. |
- Zhang, Mingfeng, et al.
(författare)
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Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:41, s. 66328-66343
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10(-15)), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10(-9)) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10(-8)). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10(-8)). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10(-4)-2.0x10(-3)). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
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