| 1. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 2. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
- Loveday, Benjamin R., et al.
(författare)
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Application of a new net primary production methodology: a daily to annual-scale data set for the North Sea, derived from autonomous underwater gliders and satellite Earth observation
- 2022
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Ingår i: EARTH SYSTEM SCIENCE DATA. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 14:9, s. 3997-4016
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Tidskriftsartikel (refereegranskat)abstract
- Shelf seas play a key role in both the global carbon cycle and coastal marine ecosystems through the draw-down and fixing of carbon, as measured through phytoplankton net primary production (NPP). Measuring NPP in situ and extrapolating this to the local, regional, and global scale presents challenges however because of limitations with the techniques utilised (e.g. radiocarbon isotopes), data sparsity, and the inherent biogeochemical heterogeneity of coastal and open-shelf waters. Here, we introduce a new data set generated using a technique based on the synergistic use of in situ glider profiles and satellite Earth observation measurements which can be implemented in a real-time or delayedmode system (haps://doi.org/10.5285/e6974644-2026-0f94-e053-6c86abc00109; Loveday and Smyth, 2022). We apply this system to a fleet of gliders successively deployed over a 19-month time frame in the North Sea, generating an unprecedented fine-scale time series of NPP in the region. At a large scale, this time series gives close agreement with existing satellite-based estimates of NPP for the region and previous in situ estimates. What has not been elucidated before is the high-frequency, small-scale, depth-resolved variability associated with bloom phenology, mesoscale phenomena, and mixed layer dynamics.
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| 4. |
- Ray, Nicholas E., et al.
(författare)
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A review of how we assess denitrification in oyster habitats and proposed guidelines for future studies
- 2021
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Ingår i: Limnology and Oceanography. - : Wiley. - 1541-5856. ; 19:10, s. 714-731
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Forskningsöversikt (refereegranskat)abstract
- Excess nitrogen (N) loading and resulting eutrophication plague coastal ecosystems globally. Much work is being done to remove N before it enters coastal receiving waters, yet these efforts are not enough. Novel techniques to remove N from within the coastal ecosystem are now being explored. One of these techniques involves using oysters and their habitats to remove N via denitrification. There is substantial interest in incorporating oyster-mediated enhancement of benthic denitrification into N management plans and trading schemes. Measuring denitrification, however, is expensive and time consuming. For large-scale adoption of oyster-mediated denitrification into nutrient management plans, we need an accurate model that can be applied across ecosystems. Despite significant effort to measure and report rates of denitrification in oyster habitats, we are unable to create such a model, due to methodological differences between studies, incomplete data reporting, and inconsistent measurements of environmental variables that may be used to predict denitrification. To make a model that can predict denitrification in oyster habitats a reality, a common sampling and reporting scheme is needed across studies. Here, we provide relevant background on how oysters may stimulate denitrification, and the importance of oyster-mediated denitrification in remediating excess N loading to coastal systems. We then summarize methods commonly used to measure denitrification in oyster habitats, discuss the importance of various environmental variables that may be useful for predicting denitrification, and present a set of guidelines for measuring denitrification in oyster habitats, allowing development of models to support incorporation of oyster-mediated denitrification into future policy decisions.
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| 5. |
- Valente, Andre, et al.
(författare)
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A compilation of global bio-optical in situ data for ocean-colour satellite applications
- 2016
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 8:1, s. 235-252
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Tidskriftsartikel (refereegranskat)abstract
- A compiled set of in situ data is important to evaluate the quality of ocean-colour satellite-data records. Here we describe the data compiled for the validation of the ocean-colour products from the ESA Ocean Colour Climate Change Initiative (OC-CCI). The data were acquired from several sources (MOBY, BOUSSOLE, AERONET-OC, SeaBASS, NOMAD, MERMAID, AMT, ICES, HOT, GeP&CO), span between 1997 and 2012, and have a global distribution. Observations of the following variables were compiled: spectral remote-sensing reflectances, concentrations of chlorophyll a, spectral inherent optical properties and spectral diffuse attenuation coefficients. The data were from multi-project archives acquired via the open internet services or from individual projects, acquired directly from data providers. Methodologies were implemented for homogenisation, quality control and merging of all data. No changes were made to the original data, other than averaging of observations that were close in time and space, elimination of some points after quality control and conversion to a standard format. The final result is a merged table designed for validation of satellite-derived ocean-colour products and available in text format. Metadata of each in situ measurement (original source, cruise or experiment, principal investigator) were preserved throughout the work and made available in the final table. Using all the data in a validation exercise increases the number of matchups and enhances the representativeness of different marine regimes. By making available the metadata, it is also possible to analyse each set of data separately. The compiled data are available at doi: 10.1594/PANGAEA.854832 (Valente et al., 2015).
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| 6. |
- Wang, Thomas J, et al.
(författare)
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Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
- 2010
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Ingår i: Lancet. - 1474-547X. ; 376:9736, s. 180-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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