| 1. |
- Bixby, H., et al.
(author)
-
Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
-
Journal article (peer-reviewed)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
|
|
| 2. |
|
|
| 3. |
- Wuttke, Matthias, et al.
(author)
-
A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
-
In: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
-
Journal article (peer-reviewed)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
|
|
| 4. |
|
|
| 5. |
- Teumer, A, et al.
(author)
-
Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- 2019
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4130-
-
Journal article (peer-reviewed)abstract
- Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
|
|
| 6. |
- Boy, M., et al.
(author)
-
Interactions between the atmosphere, cryosphere, and ecosystems at northern high latitudes
- 2019
-
In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 19:3, s. 2015-2061
-
Journal article (peer-reviewed)abstract
- The Nordic Centre of Excellence CRAICC (Cryosphere-Atmosphere Interactions in a Changing Arctic Climate), funded by NordForsk in the years 2011-2016, is the largest joint Nordic research and innovation initiative to date, aiming to strengthen research and innovation regarding climate change issues in the Nordic region. CRAICC gathered more than 100 scientists from all Nordic countries in a virtual centre with the objectives of identifying and quantifying the major processes controlling Arctic warming and related feedback mechanisms, outlining strategies to mitigate Arctic warming, and developing Nordic Earth system modelling with a focus on short-lived climate forcers (SLCFs), including natural and anthropogenic aerosols. The outcome of CRAICC is reflected in more than 150 peer-reviewed scientific publications, most of which are in the CRAICC special issue of the journal Atmospheric Chemistry and Physics. This paper presents an overview of the main scientific topics investigated in the centre and provides the reader with a state-of-the-art comprehensive summary of what has been achieved in CRAICC with links to the particular publications for further detail. Faced with a vast amount of scientific discovery, we do not claim to completely summarize the results from CRAICC within this paper, but rather concentrate here on the main results which are related to feedback loops in climate change-cryosphere interactions that affect Arctic amplification.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Olafsson, S, et al.
(author)
-
Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations
- 2017
-
In: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 2, s. 24-
-
Journal article (peer-reviewed)abstract
- A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10−7, 4.3 × 10−9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.
|
|
| 10. |
- Kular, L, et al.
(author)
-
DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis
- 2018
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2397-
-
Journal article (peer-reviewed)abstract
- The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization provide evidence that HLA variants mediate risk for MS via changes in the HLA-DRB1 DMR that modify HLA-DRB1 expression. Meta-analysis of 14,259 cases and 171,347 controls confirms that these variants confer risk from DRB1*15:01 and also identifies a protective variant (rs9267649, p < 3.32 × 10−8, odds ratio = 0.86) after conditioning for all MS-associated variants in the region. rs9267649 is associated with increased DNA methylation at the HLA-DRB1 DMR and reduced expression of HLA-DRB1, suggesting a modulation of the DRB1*15:01 effect. Our integrative approach provides insights into the molecular mechanisms of MS susceptibility and suggests putative therapeutic strategies targeting a methylation-mediated regulation of the major risk gene.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Borgstrom, F., et al.
(author)
-
Health economic aspects of vertebral augmentation procedures
- 2015
-
In: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 26:4, s. 1239-1249
-
Research review (peer-reviewed)abstract
- We reviewed all peer-reviewed papers analysing the cost-effectiveness of vertebroplasty and balloon kyphoplasty for osteoporotic vertebral compression fractures. In general, the procedures appear to be cost effective but are very dependent upon model input details. Better data, rather than new models, are needed to answer outstanding questions. Vertebral augmentation procedures (VAPs), including vertebroplasty (VP) and balloon kyphoplasty (BKP), seek to stabilise fractured vertebral bodies and reduce pain. The aim of this paper is to review current literature on the cost-effectiveness of VAPs as well as to discuss the challenges for economic evaluation in this research area. A systematic literature search was conducted to identify existing published studies on the cost-effectiveness of VAPs in patients with osteoporosis. Only peer-reviewed published articles that fulfilled the criteria of being regarded as full economic evaluations including both morbidity and mortality in the outcome measure in the form of quality-adjusted life years (QALYs) were included. The search identified 949 studies, of which four (0.4 %) were identified as relevant with one study added later. The reviewed studies differed widely in terms of study design, modelling framework and data used, yielding different results and conclusions regarding the cost-effectiveness of VAPs. Three out of five studies indicated in the base case results that VAPs were cost effective compared to non-surgical management (NSM). The five main factors that drove the variations in the cost-effectiveness between the studies were time horizon, quality of life effect of treatment, offset time of the treatment effect, reduced number of bed days associated with VAPs and mortality benefit with treatment. The cost-effectiveness of VAPs is uncertain. In answering the remaining questions, new cost-effectiveness analysis will yield limited benefit. Rather, studies that can reduce the uncertainty in the underlying data, especially regarding the long-term clinical outcomes of VAPs, should be conducted.
|
|
| 15. |
- Hátún, Hjálmar, et al.
(author)
-
An inflated subpolar gyre blows life toward the northeastern Atlantic
- 2016
-
In: Progress in Oceanography. - 0079-6611. ; 147, s. 49-66
-
Journal article (peer-reviewed)abstract
- Deep convection in the Labrador and Irminger Seas inflates the cold and low-saline subpolar gyre, which is a rich nutrient and zooplankton source for the surrounding warmer waters of subtropical origin. The zooplankton abundances on the south Iceland shelf show characteristic sub-decadal variability, which closely reflect the oceanic abundances of the ecologically most important zooplankton species – Calanus finmarchicus. Much higher abundances of this species are observed during years when the winter mixed layer depths (MLD) in the Labrador-Irminger Sea, and over the Reykjanes Ridge are deep. Furthermore, a tight relationship is identified between on-shelf zooplankton abundances and lateral shifts of the biologically productive subarctic front southwest of Iceland. Thus, we suggest that northeastward expansion of the subpolar gyre results in biologically productive periods in the waters southwest of Iceland – both oceanic and on the shelf. In addition to local atmospheric forcing, we find that the MLD and frontal position are also impacted by remote heat losses and convection in the Labrador Sea, through northward advection of unstable mode waters. The sub-decadal oceanic and on-shelf biological production peaks are possibly predictable by half a year (local winter convection to subsequent summer production), and the advective time-lag from the Labrador Sea might induce an even longer predictability horizon (up to 1.5 years).
|
|
| 16. |
- Hatun, H., et al.
(author)
-
The subpolar gyre regulates silicate concentrations in the North Atlantic
- 2017
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Journal article (peer-reviewed)abstract
- The North Atlantic is characterized by diatom-dominated spring blooms that results in significant transfer of carbon to higher trophic levels and the deep ocean. These blooms are terminated by limiting silicate concentrations in summer. Numerous regional studies have demonstrated phytoplankton community shifts to lightly-silicified diatoms and non-silicifying plankton at the onset of silicate limitation. However, to understand basin-scale patterns in ecosystem and climate dynamics, nutrient inventories must be examined over sufficient temporal and spatial scales. Here we show, from a new comprehensive compilation of data from the subpolar Atlantic Ocean, clear evidence of a marked pre-bloom silicate decline of 1.5-2 mu M throughout the winter mixed layer during the last 25 years. This silicate decrease is primarily attributed to natural multi-decadal variability through decreased winter convection depths since the mid-1990s, a weakening and retraction of the subpolar gyre and an associated increased influence of nutrient-poor water of subtropical origin. Reduced Arctic silicate import and the projected hemispheric-scale climate change-induced weakening of vertical mixing may have acted to amplify the recent decline. These marked fluctuations in pre-bloom silicate inventories will likely have important consequences for the spatial and temporal extent of diatom blooms, thus impacting ecosystem productivity and ocean-atmosphere climate dynamics.
|
|
| 17. |
- Helgadottir, Anna, et al.
(author)
-
Genome-wide analysis yields new loci associating with aortic valve stenosis
- 2018
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
-
Journal article (peer-reviewed)abstract
- Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.
|
|
| 18. |
- Jonsson, Lina, 1982, et al.
(author)
-
Rare and Common Variants Conferring Risk of Tooth Agenesis
- 2018
-
In: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 97:5, s. 515-522
-
Journal article (peer-reviewed)abstract
- We present association results from a large genome-wide association study of tooth agenesis (TA) as well as selective TA, including 1,944 subjects with congenitally missing teeth, excluding third molars, and 338,554 controls, all of European ancestry. We also tested the association of previously identified risk variants, for timing of tooth eruption and orofacial clefts, with TA. We report associations between TA and 9 novel risk variants. Five of these variants associate with selective TA, including a variant conferring risk of orofacial clefts. These results contribute to a deeper understanding of the genetic architecture of tooth development and disease. The few variants previously associated with TA were uncovered through candidate gene studies guided by mouse knockouts. Knowing the etiology and clinical features of TA is important for planning oral rehabilitation that often involves an interdisciplinary approach.
|
|
| 19. |
|
|
| 20. |
- Vignelles, D., et al.
(author)
-
Balloon-borne measurement of the aerosol size distribution from an Icelandic flood basalt eruption
- 2016
-
In: Earth and Planetary Science Letters. - : Elsevier BV. - 1385-013X .- 0012-821X. ; 453, s. 252-259
-
Journal article (peer-reviewed)abstract
- We present in situ balloon-borne measurements of aerosols in a volcanic plume made during the Holuhraun eruption (Iceland) in January 2015. The balloon flight intercepted a young plume at 8 km distance downwind from the crater, where the plume is 15 min of age. The balloon carried a novel miniature optical particle counter LOAC (Light Optical Aerosol Counter) which measures particle number concentration and size distribution in the plume, alongside a meteorological payload. We discuss the possibility of calculating particle flux by combining LOAC data with measurements of sulfur dioxide flux by ground-based UV spectrometer (DOAS). The balloon passed through the plume at altitude range of 2.0-3.1 km above sea level (a.s.l.). The plume top height was determined as 2.7-3.1 km a.s.l., which is in good agreement with data from Infrared Atmospheric Sounding Interferometer (IASI) satellite. Two distinct plume layers were detected, a non condensed lower layer (300 m thickness) and a condensed upper layer (800 m thickness). The lower layer was characterized by a lognormal size distribution of fine particles (0.2 mu m diameter) and a secondary, coarser mode (2.3 mu m diameter), with a total particle number concentration of around 100 cm(-3) in the 0.2-100 mu m detection range. The upper layer was dominated by particle centered on 20 mu m in diameter as well as containing a finer mode (2 mu m diameter). The total particle number concentration in the upper plume layer was an order of magnitude higher than in the lower layer. We demonstrate that intercepting a volcanic plume with a meteorological balloon carrying LOAC is an efficient method to characterize volcanic aerosol properties. During future volcanic eruptions, balloon borne measurements could be carried out easily and rapidly over a large spatial area in order to better characterize the evolution of the particle size distribution and particle number concentrations in a volcanic plume.
|
|
| 21. |
|
|
| 22. |
- de Jong, Yde, et al.
(author)
-
PESI - a taxonomic backbone for Europe
- 2015
-
In: Biodiversity Data Journal. - 1314-2836 .- 1314-2828. ; 3, s. 1-51
-
Journal article (peer-reviewed)abstract
- Reliable taxonomy underpins communication in all of biology, not least nature conservation and sustainable use of ecosystem resources. The flexibility of taxonomic interpretations, however, presents a serious challenge for end-users of taxonomic concepts. Users need standardised and continuously harmonised taxonomic reference systems, as well as high-quality and complete taxonomic data sets, but these are generally lacking for non-specialists. The solution is in dynamic, expertly curated web-based taxonomic tools.The Pan-European Species-directories Infrastructure (PESI) worked to solve this key issue by providing a taxonomic e-infrastructure for Europe. It strengthened the relevant social (expertise) and information (standards, data and technical) capacities of five major community networks on taxonomic indexing in Europe, which is essential for proper biodiversity assessment and monitoring activities. The key objectives of PESI were: 1) standardisation in taxonomic reference systems, 2) enhancement of the quality and completeness of taxonomic data sets and 3) creation of integrated access to taxonomic information.This paper describes the results of PESI and its future prospects, including the involvement in major European biodiversity informatics initiatives and programs.
|
|
| 23. |
|
|
| 24. |
- Sangaré, Lamba Omar, et al.
(author)
-
In Vivo CRISPR Screen Identifies TgWIP as a Toxoplasma Modulator of Dendritic Cell Migration
- 2019
-
In: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 26:4, s. 478-492
-
Journal article (peer-reviewed)abstract
- Toxoplasma can reach distant organs, especially the brain, leading to a lifelong chronic phase. However, genes involved in related in vivo processes are currently unknown. Here, we use focused CRISPR libraries to identify Toxoplasma genes that affect in vivo fitness. We focus on TgWIP, whose deletion affects Toxoplasmadissemination to distant organs. We show that TgWIP is secreted into the host cell upon invasion and interacts with the host WAVE regulatory complex and SHP2 phosphatase, both of which regulate actin dynamics. TgWIP affects the morphology of dendritic cells and mediates the dissolution of podosomes, which dendritic cells use to adhere to extracellular matrix. TgWIP enhances the motility and transmigration of parasitized dendritic cells, likely explaining its effect on in vivofitness. Our results provide a framework for systemic identification of Toxoplasmagenes with in vivo effects at the site of infection or on dissemination to distant organs, including the brain.
|
|
| 25. |
|
|
