| 1. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 2. |
- 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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| 3. |
- 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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| 4. |
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| 5. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 6. |
- 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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| 7. |
- Viktorsson, Lena, 1980, et al.
(författare)
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Recycling and burial of phosphorus in sediments of an anoxic fjord - The By Fjord, western Sweden
- 2013
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Ingår i: Journal of Marine Research. - : Journal of Marine Research/Yale. - 0022-2402 .- 1543-9542. ; 71:5, s. 351-374
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Tidskriftsartikel (refereegranskat)abstract
- Recycling and burial of sediment phosphorus were studied in the By Fjord, western Sweden, during the years 2009 to 2010 using autonomous benthic landers and sediment sampling. The By Fjord is a small fjord with a shallow sill at its narrow mouth, which limits water exchange of the fjord’s basin water. The water in the basin is exchanged only every 3 to 5 years and the water below sill level is anoxic or sulfidic between water renewals. Five sites were examined in the By Fjord; three shallow sites above the sill level with oxic bottom waters and two deeper sites with anoxic bottom waters. Contents of sediment organic carbon and total nitrogen were higher at deep stations when compared to shallow stations, whereas the contents of sediment inorganic P was higher, and sediment organic P generally lower, at shallow than at deep stations both in surficial and buried sediment. One shallow oxic site and one deep anoxic site were also examined in the adjacent Koljo Fjord having similar characteristics as the By Fjord. In situ measurements of benthic fluxes of dissolved inorganic phosphorus (DIP) showed that the fluxes from sediments with oxic overlying water (0.05–0.23 mmol m−2 d−1) were much lower than fluxes from sediments with anoxic overlying water (1.25–2.26 mmol m−2 d−1). The DIP flux increased with increasing flux of dissolved inorganic carbon (DIC) not only at anoxic but also at oxic bottoms, which is different from observations in brackish water environments. The average ratio between the DIC and DIP fluxes at oxic bottoms was almost 10 times higher than the Redfield C:P ratio indicating partial immobilization of P in oxic sediments. In contrast, the C:P ratio in fluxes was on average 1.5 times lower than Redfield at the anoxic bottoms. The benthic fluxes from anoxic bottoms were P rich not only in relation to C, but also to N. The low C:P flux ratio at anoxic sites coincided with a ≈ 2.5 times higher than Redfield C:P ratio of organic matter in the sediment solid phase clearly suggesting preferential regeneration of P at anoxic bottoms. Burial of inorganic P was higher than organic P burial at both anoxic and oxic sites; the former made up 59 to 60% of the total P burial at the deep anoxic stations, and 80% at the main shallow oxic station. The burial efficiency for organic P at anoxic bottoms was estimated to be only 1 to 3%, which indicates extremely efficient recycling of deposited organic P under anoxic conditions in this fjord environment.
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| 8. |
- Almroth Rosell, Elin, 1977, et al.
(författare)
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Effects of simulated natural and massive resuspension on benthic oxygen, nutrient and dissolved inorganic carbon fluxes in Loch Creran, Scotland
- 2012
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Ingår i: Journal of Sea Research. - : Elsevier BV. - 1385-1101. ; 72, s. 38-48
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Tidskriftsartikel (refereegranskat)abstract
- The effect of repeated natural resuspension on benthic oxygen consumption and the effect of natural and massive resuspension on oxygen consumption and fluxes of phosphate, silicate, ammonium and dissolved inorganic carbon (DIC) were studied at two stations (S1 and S2) in a Scottish sea loch. Station S11 had organically enriched sediment and station S1 had lower organic content in the sediment. The fluxes were measured in situ using the Göteborg benthic lander. Natural resuspension, simulating resuspension events due to strong wind, waves or currents, and massive resuspension, simulating resuspension due to e.g. trawling or dredging, were created inside the incubation chambers by regulating the stirring of the incubated overlying water or by retracting and shaking the incubated sediment. Natural resuspension showed clear effects on the oxygen consumption at station S11, where it increased with an average of 12.8 (standard error (s.e.) 0.17) and 7.7 (s.e. 0.12) mmol m− 2 d− 1 during the first and second incubations, respectively. At station S1 there was no clear effect of natural resuspension on the oxygen consumption. Massive resuspension increased the oxygen consumption on S1 with an average of 608 (standard deviation (sd) 366) mmol m− 2 d− 1 and on S11 with an average of 2396 (sd 2265) mmol m− 2 d− 1. The fluxes of ammonium, phosphate and silicate were affected by the massive resuspension in 50, 14 and 33% of the chambers, respectively, on station S11. However, in the majority of the cases there were no effects on the nutrient and DIC fluxes of massive resuspension. The absolute concentrations of DIC, ammonium and silicate did however instantly increase with an average of 419 (sd 297), 48 (sd 27) and 6.9 (sd 3.7) μM, respectively, at S11 upon massive resuspension. The concentrations of phosphate decreased instantly with an average of 0.2 (sd 0.1) μM. On station S1 there were effects only on the ammonium and silicate concentrations, which increased with 0.8 (sd 0.3) and 1.13 (sd 0.36) μM, respectively. The large increase in oxygen consumption due to massive resuspension indicates that activities like e.g. trawling and dredging that take place in areas where water exchange occurs infrequently may lead to oxygen depletion in bottom water, which in turn might affect the ecological balance. Silicate, ammonium and DIC can be released due to massive resuspension and contribute to increased algal blooms in surface waters.
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| 9. |
- Almroth Rosell, Elin, 1977, et al.
(författare)
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Transport of fresh and resuspended particulate organic material in the Baltic Sea — a model study
- 2011
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Ingår i: Journal of Marine Systems. - : Elsevier BV. - 0924-7963. ; 87:1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- A fully coupled high-resolution 3-dimensional biogeochemical–physical ocean model including an empirical wave model was used to investigate the long-term average (1970–2007) distributions and transports of resuspended matter and other types of suspended organic matter in the Baltic Sea. Modelled bottom types were compared to observations and the results showed that the model successfully managed to capture the horizontal, as well as the vertical, distribution of the different bottom types: accumulation, transport and erosion bottoms. The model also captured well the nutrient element contents in the sediments. On average the largest contribution of resuspended organic carbon to the transport of total organic carbon is found at erosion and transport bottoms. Although the relative transport of resuspended organic carbon at deeper accumulation bottoms in general is low (< 10% of total), the central parts of the sub-basins act on average as sinks that import organic matter while the more shallow areas and the coastal regions acts as sources of organic carbon in the water column. This indicates that the particulate organic matter produced in erosion and transport areas might be kept in suspension long enough to be transported and settle in less energetic areas, i.e. on accumulation bottoms.
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| 10. |
- Atamanchuk, Dariia, 1987, et al.
(författare)
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Performance of a lifetime-based optode for measuring partial pressure of carbon dioxide in natural waters
- 2014
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Ingår i: Limnology and Oceanography : Methods. - : Wiley. - 1541-5856. ; 12, s. 63-73
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Tidskriftsartikel (refereegranskat)abstract
- This article reports the performance of an improved, newly developed, compact, low power, lifetime-based optical sensor (optode) for measuring partial pressure of dissolved CO2 gas (pCO2) in natural waters. The results suggest that after preconditioning, these sensors are stable in water for time periods longer than 7 months. The wide dynamic range of about 0-50000 μatm opens possibilities for numerous applications of which some are presented. In normal marine environments with pCO2 levels of 200-1000 μatm, the best-obtained precision was about ±2 μatm, and the absolute accuracy was between 2-75 μatm, depending on the deployment and the quality of the collected reference water samples. One limitation is that these sensors will become irreversibly poisoned by H2S and should thus not be deployed in sulphidic environments.
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