| 1. |
- Saevarsdottir, S., et al.
(author)
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Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
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Journal article (peer-reviewed)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
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| 2. |
- Uusitupa, M., et al.
(author)
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Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome : a randomized study (SYSDIET)
- 2013
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 274:1, s. 52-66
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Journal article (peer-reviewed)abstract
- Background Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. Methods We conducted a randomized dietary study lasting for 18-24weeks in individuals with features of metabolic syndrome (mean age 55years, BMI 31.6kgm-2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. Results Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmolL-1 95% CI -0.35; -0.01, P=0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P=0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P=0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37ngL-1, P= 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P=0.049) and magnesium (mg, -0.23, -0.41; -0.05, P=0.012) were associated with IL-1 Ra. Conclusions Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.
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| 3. |
- Rixen, C., et al.
(author)
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Winters are changing: snow effects on Arctic and alpine tundra ecosystems
- 2022
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In: Arctic Science. - : Canadian Science Publishing. - 2368-7460. ; 8:3, s. 572 - 608
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Journal article (peer-reviewed)abstract
- Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions, and moisture availability during winter. It also affects the growing season's start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover's role for vegetation, plant-animal interactions, permafrost conditions, microbial processes, and biogeochemical cycling. We also compare studies of natural snow gradients with snow experimental manipulation studies to assess time scale difference of these approaches. The number of tundra snow studies has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. Specifically, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by snow addition and snow removal manipulations (average 7.9 days advance and 5.5 days delay, respectively) were substantially lower than the temporal variation over natural spatial gradients within a given year (mean range 56 days) or among years (mean range 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates.
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| 4. |
- Maes, S.L., et al.
(author)
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Environmental drivers of increased ecosystem respiration in a warming tundra
- 2024
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 629:8010, s. 105-113
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Journal article (peer-reviewed)abstract
- Arctic and alpine tundra ecosystems are large reservoirs of organic carbon. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain. This hampers the accuracy of global land carbon–climate feedback projections. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9–2.0 °C] in air and 0.4 °C [CI 0.2–0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22–38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.
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| 5. |
- Collins, C. G., et al.
(author)
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Experimental warming differentially affects vegetative and reproductive phenology of tundra plants
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Rapid climate warming is altering Arctic and alpine tundra ecosystem structure and function, including shifts in plant phenology. While the advancement of green up and flowering are well-documented, it remains unclear whether all phenophases, particularly those later in the season, will shift in unison or respond divergently to warming. Here, we present the largest synthesis to our knowledge of experimental warming effects on tundra plant phenology from the International Tundra Experiment. We examine the effect of warming on a suite of season-wide plant phenophases. Results challenge the expectation that all phenophases will advance in unison to warming. Instead, we find that experimental warming caused: (1) larger phenological shifts in reproductive versus vegetative phenophases and (2) advanced reproductive phenophases and green up but delayed leaf senescence which translated to a lengthening of the growing season by approximately 3%. Patterns were consistent across sites, plant species and over time. The advancement of reproductive seasons and lengthening of growing seasons may have significant consequences for trophic interactions and ecosystem function across the tundra. It is unclear whether climate driven phenological shifts of tundra plants are consistent across the plant growing season. Here the authors analyse data from a network of field warming experiments in Arctic and alpine tundra, finding that warming differentially affects the timing and duration of reproductive and vegetative phenology.
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| 6. |
- Prevey, J. S., et al.
(author)
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Warming shortens flowering seasons of tundra plant communities
- 2019
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In: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 3:1, s. 45-52
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Journal article (peer-reviewed)abstract
- Advancing phenology is one of the most visible effects of climate change on plant communities, and has been especially pronounced in temperature-limited tundra ecosystems. However, phenological responses have been shown to differ greatly between species, with some species shifting phenology more than others. We analysed a database of 42,689 tundra plant phenological observations to show that warmer temperatures are leading to a contraction of community-level flowering seasons in tundra ecosystems due to a greater advancement in the flowering times of late-flowering species than early-flowering species. Shorter flowering seasons with a changing climate have the potential to alter trophic interactions in tundra ecosystems. Interestingly, these findings differ from those of warmer ecosystems, where early-flowering species have been found to be more sensitive to temperature change, suggesting that community-level phenological responses to warming can vary greatly between biomes.
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| 7. |
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| 8. |
- Thorgeirsson, T. E., et al.
(author)
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A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences
- 2016
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:5, s. 594-600
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Journal article (peer-reviewed)abstract
- Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency = 0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P = 1.2 x 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P = 4.0 x 10(-4)), chronic obstructive pulmonary disease (COPD; P = 9.3 x 10(-4)), peripheral artery disease (PAD; P = 0.090) and abdominal aortic aneurysms (AAAs; P = 0.12), and the variant associates strongly with the early-onset forms of LC (OR = 4.49, P = 2.2 x 10(-4)), COPD (OR = 3.22, P = 2.9 x 10(-4)), PAD (OR = 3.47, P = 9.2 x 10(-3)) and AAA (OR = 6.44, P = 6.3 x 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P = 6.8 x 10(-5)), particularly for early-onset cases (P = 2.1 x 10(-7)). Our results are in agreement with functional studies showing that the human alpha 4 beta 2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.
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| 9. |
- Gislason, S.R., et al.
(author)
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Environmental pressure from the 2014–15 eruption of Bárðarbunga volcano, Iceland
- 2015
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In: Geochemical Perspectives Letters. - : European Association of Geochemistry. - 2410-3403 .- 2410-339X. ; 1:2015, s. 84 - 93
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Journal article (peer-reviewed)abstract
- The effusive six months long 2014-2015 Bárðarbunga eruption (31 August-27 February) was the largest in Iceland for more than 200 years, producing 1.6 ± 0.3 km3 of lava. The total SO2 emission was 11 ± 5 Mt, more than the amount emitted from Europe in 2011. The ground level concentration of SO2 exceeded the 350 μg m−3 hourly average health limit over much of Iceland for days to weeks. Anomalously high SO2 concentrations were also measured at several locations in Europe in September. The lowest pH of fresh snowmelt at the eruption site was 3.3, and 3.2 in precipitation 105 km away from the source. Elevated dissolved H2SO4, HCl, HF, and metal concentrations were measured in snow and precipitation. Environmental pressures from the eruption and impacts on populated areas were reduced by its remoteness, timing, and the weather. The anticipated primary environmental pressure is on the surfacewaters, soils, and vegetation of Iceland.
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| 10. |
- Hollister, R. D., et al.
(author)
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A review of open top chamber (OTC) performance across the ITEX Network
- 2023
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In: Arctic Science. - : Canadian Science Publishing. - 2368-7460. ; 9:2, s. 331-344
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Journal article (peer-reviewed)abstract
- Open top chambers (OTCs) were adopted as the recommended warming mechanism by the International Tundra Experiment network in the early 1990s. Since then, OTCs have been deployed across the globe. Hundreds of papers have reported the im-pacts of OTCs on the abiotic environment and the biota. Here, we review the impacts of the OTC on the physical environment, with comments on the appropriateness of using OTCs to characterize the response of biota to warming. The purpose of this review is to guide readers to previously published work and to provide recommendations for continued use of OTCs to under -stand the implications of warming on low stature ecosystems. In short, the OTC is a useful tool to experimentally manipulate temperature; however, the characteristics and magnitude of warming varies greatly in different environments; therefore, it is important to document chamber performance to maximize the interpretation of biotic response. When coupled with long-term monitoring, warming experiments are a valuable means to understand the impacts of climate change on natural ecosystems.
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