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- Wang, Z., et al.
(författare)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Tidskriftsartikel (refereegranskat)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 3. |
- 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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- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 5. |
- Braungardt, C. B., et al.
(författare)
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Analysis of dissolved metal fractions in coastal waters: An inter-comparison of five voltammetric in situ profiling (VIP) systems
- 2009
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Ingår i: Marine Chemistry. - : Elsevier BV. - 0304-4203. ; 114:1-2, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the results of an inter-comparison exercise undertaken to test the reliability and performance of a voltammetric in situ profiling system (VIP system) and carried out by partners based in Italy, Sweden, Switzerland and the UK. The VIP system was designed to allow in situ simultaneous monitoring of the dynamic fractions (i.e. the maximum potentially bioavailable fractions) of Cu(II). Pb(II) and Cd(II) in natural waters at a frequency of 2-3 analyses h(-1). The four participating groups used the VIP systems under laboratory conditions to determine dissolved concenterations of Cu, Pb and Cd in river, estuarine and coastal water reference materials (SLRS-3/4, SLEW-2/3 and CASS3/4, respectively). The accuracy of the VIP method was comparable to that of established methodologies, including inductively coupled plasma mass spectrometry and voltammetric methods using mercury-electrodes. The VIP systems were also applied to determine the dynamic fractions of the target analytes in freshly collected samples ex situ, as well as in situ in contrasting European marine waters. There was good agreement between the concentrations of the dynamic metal fractions determined in laboratory analyses, and observed during the Simultaneous deployment of up to five VIP instruments for periods of several hours in coastal waters. The simultaneous in situ deployment of two VIP instruments in an estuary showed a consistent analytical performance over several days of continuous operation. The results of this inter-comparison exercise show that the VIP system is a reliable submersible probe for accurate, sensitive and high resolution in situ monitoring of dissolved metal fractions in the picomolar (Cd, Pb) and nanomolar (Cu) concentration ranges. (C) 2009 Elsevier B.V. All rights reserved.
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| 6. |
- Cortes, Andres J., et al.
(författare)
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Small-scale patterns in snowmelt timing affect gene flow and the distribution of genetic diversity in the alpine dwarf shrub Salix herbacea
- 2014
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Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 113:3, s. 233-239
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Tidskriftsartikel (refereegranskat)abstract
- Current threats to biodiversity, such as climate change, are thought to alter the within-species genetic diversity among microhabitats in highly heterogeneous alpine environments. Assessing the spatial organization and dynamics of genetic diversity within species can help to predict the responses of organisms to environmental change. In this study, we evaluated whether small-scale heterogeneity in snowmelt timing restricts gene flow between microhabitats in the common long-lived dwarf shrub Salix herbacea L. We surveyed 273 genets across 12 early-and late-snowmelt sites (that is, ridges and snowbeds) in the Swiss Alps for phenological variation over 2 years and for genetic variation using seven SSR markers. Phenological differentiation triggered by differences in snowmelt timing did not correlate with genetic differentiation between microhabitats. On the contrary, extensive gene flow appeared to occur between microhabitats and slightly less extensively among adjacent mountains. However, ridges exhibited significantly lower levels of genetic diversity than snowbeds, and patterns of effective population size (Ne) and migration (Nem) between microhabitats were strongly asymmetric, with ridges acting as sources and snowbeds as sinks. As no recent genetic bottlenecks were detected in the studied sites, this asymmetry is likely to reflect current metapopulation dynamics of the species dominated by gene flow via seeds rather than ancient re-colonization after the last glacial period. Overall, our results suggest that seed dispersal prevents snowmelt-driven genetic isolation, and snowbeds act as sinks of genetic diversity. We discuss the consequences of such small-scale variation in gene flow and diversity levels for population responses to climate change.
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| 7. |
- Illuminati, S., et al.
(författare)
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In-situ trace metal (Cd, Pb, Cu) speciation along the Po River plume (Northern Adriatic Sea) using submersible systems
- 2019
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Ingår i: Marine Chemistry. - : Elsevier BV. - 0304-4203. ; 212, s. 47-63
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Tidskriftsartikel (refereegranskat)abstract
- Information on the distribution and speciation of trace metals is of critical importance for our ability to interpret the links between the bioavailability and uptake of an element, and its biogeochemical cycle in coastal environments. Within the framework of the European Project "In-situ automated Monitoring of Trace metal speciation in Estuaries and Coastal zones in relation with the biogeochemical processes (IMTEC)", the chemical speciation of Cd, Pb and Cu was carried out along the Po River plume in the period 27 October - 2 November 2002. During the cruise, five Voltammetric In-situ Profiling systems and one Multi Physical Chemical Profiler, as well as conventional voltammetric instruments, were successfully applied in order to evaluate the distribution of Cd, Pb and Cu between different fractions (free ion, dynamic, colloidal, dissolved and particulate fractions) and to assess the evolution of these fractions during estuarine mixing and in the water column. Dynamic concentrations were 0.05-0.2 nmol L-1 Cd, 0.02-0.2 nmol L-1 Pb, and 0.15-4.0 nmol L-1 Cu. Cd was mainly present as dynamic fraction (40-100% of the dissolved Cd). High proportions of Pb (similar to 70%) and Cu (similar to 80%) were present as colloids probably of biogenic origin. Principal components analysis reveals a strong influence of the Po River discharge on the spatial and vertical distributions of metal species. Almost all the metal fractions globally decreased following the salinity gradient. Metal concentrations are far below (at least one order of magnitude lower) the Environmental Quality Standard established by the Italian law. However, the Cu dynamic fraction showed concentrations likely to be toxic to sensitive phytoplankton community and to have negative effects on larva development of coastal macroinvertebrate species (toxicity data extracted from literature).
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