| 1. |
- Barrett, Jennifer H., et al.
(författare)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 2. |
- Iles, Mark M., et al.
(författare)
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A variant in FTO shows association with melanoma risk not due to BMI
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:4, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanomasusceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
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| 3. |
- MacGregor, Stuart, et al.
(författare)
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Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1114-1118
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 x 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 x 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.
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| 4. |
- Amos, Christopher I, et al.
(författare)
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Genome-wide association study identifies novel loci predisposing to cutaneous melanoma
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:24, s. 23-5012
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Tidskriftsartikel (refereegranskat)abstract
- We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.
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| 5. |
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| 6. |
- Bergman, Inger, et al.
(författare)
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The influence of sulphate deposition on the seasonal variation of peat pore water methyl Hg in a boreal mire
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9, s. e45547-
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we investigate the hypothesis that long-term sulphate (SO42-) deposition has made peatlands a larger source of methyl mercury (MeHg) to remote boreal lakes. This was done on experimental plots at a boreal, low sedge mire where the effect of long-term addition of SO42- on peat pore water MeHg concentrations was observed weekly throughout the snow-free portion of 1999. The additions of SO42- started in 1995. The seasonal mean of the pore water MeHg concentrations on the plots with 17 kg ha(-1) yr(-1) of sulphur (S) addition (1.3 +/- 0.08 ng L-1, SE; n=44) was significantly (p<0.0001) higher than the mean MeHg concentration on the plots with 3 kg ha(-1) yr(-1) of ambient S deposition (0.6 +/- 0.02 ng L-1, SE; n=44). The temporal variation in pore water MeHg concentrations during the snow free season was larger in the S-addition plots, with an amplitude of >2 ng L-1 compared to +/-0.5 ng L-1 in the ambient S deposition plots. The concentrations of pore water MeHg in the S-addition plots were positively correlated (r(2)=0.21; p=0.001) to the groundwater level, with the lowest concentrations of MeHg during the period with the lowest groundwater levels. The pore water MeHg concentrations were not correlated to total Hg, DOC concentration or pH. The results from this study indicate that the persistently higher pore water concentrations of MeHg in the S-addition plots are caused by the long-term additions of SO42- to the mire surface. Since these waters are an important source of runoff, the results support the hypothesis that SO42- deposition has increased the contribution of peatlands to MeHg in downstream aquatic systems. This would mean that the increased deposition of SO42- in acid rain has contributed to the modern increase in the MeHg burdens of remote lakes hydrologically connected to peatlands.
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| 8. |
- Bishop, Kevin, 1960-, et al.
(författare)
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Forest Cover and Stream Flow in a Headwater of the Blue Nile : Complementing Observational Data Analysis with Community Perception
- 2010
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 39:4, s. 284-294
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Tidskriftsartikel (refereegranskat)abstract
- This study analyses the relation of forest cover and stream flow on the 266 km2 Koga watershed in the headwaters of Blue Nile Basin using both observed hydrological data and community perception. The watershed went from 16% forest cover in 1957 to 1% by 1986. The hydrological record did not reveal changes in the flow regime between 1960 and 2002 despite the reduction in forest area. This agrees with the perception of the downstream community living near the gauging station. The upstream community, however, reported both decreases in low flows and increases in high flows shortly after the forest cover was reduced. The upstream deforestation effect appeared to have been buffered by a wetland lower in the watershed. This study concludes that community perception can be a complement to observational data for better understanding how forest cover influences the flow regime.
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| 9. |
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| 10. |
- Bishop, Kevin, et al.
(författare)
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Relation between land use change for long- term trends of organic carbon in lake water and its importance for acidification assessment
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This study examines the changes of total organic carbon (TOC) concentrations in 20 Swedish lakes throughout Sweden using pre-industrial (1860) TOC0 inferred from near-infrared spectrometry (TOCNIRS) of lake sediments to determine if land use change over time could be a plausible explanation for changes in lake water TOC. The study also focuses on the importance of using inferred pre-industrial data of lake water pH and TOC for acidification assessment, in particular ANC0. Most lakes in this study show a long-term decreasing trend of TOC from 1860 up to -0.45 mg/l/yr-1 to an identified breaking point where the TOC turns from decreasing to increasing. Fifteen of the lakes have a breaking point in the mid to late 20th century (1950-1980) while five lakes do not display a clear breaking point. The magnitude of the increasing trend of TOC after the breaking point is up to 0.16 mg/l/yr-1 . Changes in land use were studied by comparing historical maps with present databases of land use. Land use changes in the catchment area show substantial differences in forest cultivation; for instance the coniferous forest has increased by 26% on average. This increase is due to removal of native forest (deciduous forest) and removal of wetlands. Two major conclusions can be drawn from the effects of land use change on TOC levels: (I) No direct correlation between land use change and long-term trends of TOC could be identified in this study. Previous studies have identified the effects of land use change on the carbon storage in the catchment area that corresponds well with the findings of this study. (II) the character of the forest land plays an important role when discussing the effects of land use change for long term TOC trends. The change from open-ended forests with large trees to intense managed forest is considered as an important driving force for TOC. To determine reference conditions there is a need to make good estimations of ANC0 for acidification assessment in Swedish lakes. This study examines the precision of MAGIC model ANC0 calculations (ANC0-MAGIC) against ANC0 calculated with TOCNIRS, diatom-pH and calculated pCO2 (ANC0, diatom-NIRS). ANC0, diatom-NIRS shows a mean difference of (-31µeq/l) when comparing it with ANC0-MAGIC. In comparison, when using contemporary TOC (TOCt) mean lake value 1990-2005 (ANC0,diatom-TOC) the results show a mean difference of (-0.45 µeq/l) in comparison with ANC0-MAGIC. A better fit is generated with TOCNIRS then TOCt. This could be an indication that ANC0- MAGIC overestimates the acidification of Swedish lakes. The European Union’s “Water 8 Framework Directive”, which Sweden has implemented, requires that all surface waters within the Union’s authority have achieved good ecological status by 2015. According to the ecological quality standard the differences between the pre-industrial pH and contemporary pH, i.e. ΔpH=pH0-pHt, should not be more than 0.4 units. This study shows that the long-term trends have to be accounted for when calculating reference conditions and ecological status for acidification
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