| 1. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 2. |
- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 3. |
- Blythe, L. S., et al.
(författare)
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Viscosity controlled magma-carbonate interaction : a comparison of Mt. Vesuvius (Italy) and Mt. Merapi (Indonesia)
- 2012
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Konferensbidrag (refereegranskat)abstract
- Magma-carbonate interaction is increasingly seen as a viable and extremely important cause of magma contamination, and the generation of a crustally sourced CO2 phase (Goff et al., 2001; Freda et al., 2010). Even though the process is well recognized at certain volcanoes e.g. Popocatépetl, (Mexico); Merapi, (Indonesia); and Colli Albani, (Italy) (Goff et al., 2001; Deegan et al., 2010; Freda et al., 2010), neither the kinetics of carbonate assimilation nor its consequences for controlling the explosivity of eruptions have been constrained. Here we show the results of magma-carbonate interaction experiments conducted at 1200 °C and 0.5 GPa for varying durations (0 s, 60 s, 90 s and 300 s) for the Mt. Merapi (Indonesia) and Mt. Vesuvius (Italy) volcanic systems. We performed experiments using glassy starting materials specific to each volcano (shoshonite for Mt. Vesuvius, basaltic-andesite for Mt. Merapi) with different degrees of hydration (anhydrous vs hydration with ~ 2 wt % water) and using carbonate fragments of local origin; see Deegan et al., (2010) and Jolis et al., (2011). Experimental products include a gas phase (CO2-rich) and two melt phases, one pristine (Ca-normal) and one contaminated (Ca-rich) separated by a 'contamination front' which propagates outwards from the carbonate clast. Vesicles appear to nucleate in the contaminated glass and then migrate into the pristine one. Both contamination front propagation and bubble migration away from the carbonate are slower in anhydrous basaltic-andesite (Merapi anhydrous series) than in hydrated basaltic-andesite and shoshonite (Merapi and Vesuvius hydrated series), suggesting that assimilation speed is strongly controlled by the degree of hydration and the SiO2 content, both of which influence melt viscosity and hence diffusivity. As the carbonate dissolution proceeds in our experiments, initially dissolved and eventually exsolved CO2 builds up in the contaminated Ca-rich melt phase. Once melt volatile oversaturation is achieved, the reaction can only progress further if vesicles are efficiently removed from the contaminated melt phase. Viscosity, which controls the vesicle migration efficiency, thus ultimately determines the progression and rate of the contamination reaction. Our results show that characteristics of magma-carbonate interaction at different volcanic systems are likely to differ as a result of a volcanos' individual magma properties, especially viscosity, which determines the speed at which gaseous reaction products (i.e. CO2) can be removed from the reaction site.
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| 4. |
- Ganerod, M., et al.
(författare)
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Geochronology of the Tardree Rhyolite Complex, Northern Ireland : Implications for zircon fission track studies, the North Atlantic Igneous Province and the age of the Fish Canyon sanidine standard
- 2011
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Ingår i: Chemical Geology. - : Elsevier BV. - 0009-2541 .- 1872-6836. ; 286:3-4, s. 222-228
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Tidskriftsartikel (refereegranskat)abstract
- The British-Irish Palaeogene Igneous Province (BIPIP) is part of the larger North Atlantic Igneous Province and includes the lava fields of Antrim, Mull, and Skye. The Tardree Rhyolite Complex (TRC) in Northern Ireland forms an important stratigraphic unit between the Lower and Upper Basalt Formations of the Antrim Lava Group (ALG). Previous zircon age determinations obtained from the TRC have been used as a standard in zircon fission track studies, but contradict several (40)Ar/(39)Ar sanidine and U-Pb zircon results. We provide new (40)Ar/(39)Ar sanidine and U-Pb CA-TIMS zircon ages which resolve this discrepancy. Two sanidine samples from the Sandy Braes vent and the columnar-jointed dome-forming rhyolites of Tardree Forest yield a weighted mean (40)Ar/(39)Ar age of 61.13 +/- 0.42 Ma (2 sigma, internal error). Ten U-Pb CA-TIMS zircon analyses were undertaken, eight of which employed the CA-TIMS approach on both multi-grain fractions and single grains. Six of the CA-TIMS data yield a disequilibrium-corrected weighted mean (206)Pb-(238)U age of 61.32 +/- 0.09 Ma (2 sigma). The consistency of the (40)Ar/(39)Ar ages with the CA-TIMS U-Pb zircon age, points to a closed system of both K and Ar since eruption. We propose that the crystallization age of the TRC be taken as 61.32 +/- 0.09 Ma and that the currently used age of the zircon fission track standard (58.4 +/- 0.7 Ma) be changed accordingly. This also places the eruption of the TRC in magnetochron C26r, which is consistent with the reversed polarity magnetic remanence observed in the ALG, and supports the conclusion of Ganered et al. (2010) that the Lower Basalt Formation is older than the Vaigat Formation in Western Greenland. No resolvable zircon inheritance has been detected by the TIMS analyses, consistent with the fact that the temporal and geographic extent of rhyolitic magmatism within this sector of the BIPIP was very limited, and hence was unlikely to provide inherited magmatic zircons from slightly older magmas (antecrysts). Potentially older zircon xenocrysts would be derived from the underlying Caledonian basement (>400 Ma) or yet older rocks. These should be easily detectable if the Tardree zircon was to be employed as a U-Pb zircon standard. The paired (40)Ar/(39)Ar and (206)Pb-(238)U results from this study indicate an age of 28.393 +/- 0.194 Ma for the widely used Fish Canyon sanidine standard and gives further support to the recent calibrations of Kuiper et al. (2008) and Renne et al. (2010).
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| 5. |
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| 6. |
- Jolis, E. M., et al.
(författare)
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Tracing crustal contamination along the Java segment of the Sunda Arc, Indonesia
- 2012
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Konferensbidrag (refereegranskat)abstract
- Arc magmas typically display chemical and petrographic characteristics indicative of crustal input. Crustal contamination can take place either in the mantle source region or as magma traverses the upper crust (e.g. [1]). While source contamination is generally considered the dominant process (e.g. [2]), late-stage crustal contamination has been recognised at volcanic arcs too (e.g. [3]). In light of this, we aim to test the extent of upper crustal versus source contamination along the Java segment of the Sunda arc, which, due its variable upper crustal structure, is an exemplary natural laboratory. We present a detailed geochemical study of 7 volcanoes along a traverse from Anak-Krakatau in the Sunda strait through Java and Bali, to characterise the impact of the overlying crust on arc magma composition. Using rock and mineral elemental geochemistry, radiogenic (Sr, Nd and Pb) and, stable (O) isotopes, we show a correlation between upper crustal composition and the degree of upper crustal contamination. We find an increase in 87Sr/86Sr and δ18O values, and a decrease in 143Nd/144Nd values from Krakatau towards Merapi, indicating substantial crustal input from the thick continental basement present. Volcanoes to the east of Merapi and the Progo-Muria fault transition zone, where the upper crust is thinner, in turn, show considerably less crustal input in their isotopic signatures, indicating a stronger influence of the mantle source. Our new data represent a systematic and high-resolution arc-wide sampling effort that allows us to distinguish the effects of the upper crust on the compositional spectrum of individual volcanic systems along the Sunda arc. [1] Davidson, J.P, Hora, J.M, Garrison, J.M & Dungan, M.A 2005. Crustal Forensics in Arc Magmas. J. Geotherm. Res. 140, 157-170; [2] Debaille, V., Doucelance, R., Weis, D., & Schiano, P. 2005. Geochim. Cosmochim. Acta, 70,723-741; [3] Gasparon, M., Hilton, D.R., & Varne, R. 1994. Earth Planet. Sci. Lett., 126, 15-22.
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| 7. |
- Jolis, E. M., et al.
(författare)
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Tracing crustal contamination along the Java segment of the Sunda Arc, Indonesia
- 2012
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Konferensbidrag (refereegranskat)abstract
- Arc magmas typically display chemical and petrographic characteristics indicative of crustal input. Crustal contamination can take place either in the mantle source region or as magma traverses the crust (e.g. [1]). While source contamination is generally considered the dominant process (e.g. [2, 3, 4]), crustal contamination in high level magma chambers has also been recognised at volcanic arcs (e.g. [5, 6]). In light of this, we aim to test the extent of upper crustal versus source contamination along the Java segment of the Sunda arc, which, because of its variable upper crustal structure, is ideal for the task.We present a detailed geochemical study of 7 volcanoes along a traverse from Anak-Krakatau in the Sunda strait through Java (Gede, Slamet, Merapi, Kelut, Kawah-Ijen) and Bali (Batur). Using rock and mineral elemental geochemistry and radiogenic (Sr, Nd and Pb) and, stable (O) isotopes, we show a correspondence between changes in composition of the upper crust and the apparent degree of upper crustal contamination. There is an increase in 87Sr/86Sr and δ18O, and a decrease in 143Nd/144Nd from Krakatau towards Merapi, indicating substantial input from the thick quasi-continental basement beneath East and Central Java. Volcanoes to the east of Merapi, and the Progo-Muria fault zone, where the upper crust is thinner and increasingly oceanic in nature have lower 87Sr/86Sr and δ18O, and higher 143Nd/144Nd indicating a stronger influence of the mantle source [7]. Our new data represent a systematic and high-resolution arc-wide sampling effort that allows us to distinguish the effects of the upper crust on the compositional spectrum of individual volcanic systems along the Sunda arc. [1] Davidson, J.P, Hora, J.M, Garrison, J.M & Dungan, M.A (2005), J. Geotherm. Res., 140, 157-170.[2] Hilton, D.R., Fischer, T.P. & Marty, B. (2002), Rev. Mineral. Geochem., 47, 319-370.[3] Gertisser, R. & Keller, J. (2003). J. Petrol., 44, 457-489[4] Debaille, V., Doucelance, R., Weis, D., & Schiano, P. (2005), Geochim. Cosmochim. Acta, 70,723-741.[5] Gasparon, M., Hilton, D.R., & Varne, R. (1994), Earth Planet. Sci. Lett., 126, 15-22.[6] Chadwick, J.P., Troll, V.R., Ginibre, C., Morgan, D., Gertisser, R., Waight, T.E. & Davidson, J.P. (2007), J. Petrol., 48, 1793-1812.[7] Whitford, D.J. (1975), Geochim. Cosmochim. Acta, 39, 1287-1302.
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| 8. |
- Troll, Valentin R., et al.
(författare)
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Crustal CO2 liberation during the 2006 eruption and earthquake events at Merapi volcano, Indonesia
- 2012
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 39, s. L11302-
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Tidskriftsartikel (refereegranskat)abstract
- High-temperature volcanic gas is widely considered to originate from ascending, mantle-derived magma. In volcanic arc systems, crustal inputs to magmatic gases mainly occur via subducted sediments in the mantle source region. Our data from Merapi volcano, Indonesia imply, however, that during the April-October 2006 eruption significant quantities of CO2 were added from shallow crustal sources. We show that prior to the 2006 events, summit fumarole gas delta C-13((CO2)) is virtually constant (delta C-13(1994-2005) = -4.1 +/- 0.3 parts per thousand), but during the 2006 eruption and after the shallow Yogyakarta earthquake of late May, 2006 (M6.4; hypocentres at 10-15 km depth), carbon isotope ratios increased to -2.4 +/- 0.2 parts per thousand. This rise in delta C-13 is consistent with considerable addition of crustal CO2 and coincided with an increase in eruptive intensity by a factor of similar to 3 to 5. We postulate that this shallow crustal volatile input supplemented the mantle-derived volatile flux at Merapi, intensifying and sustaining the 2006 eruption. Late-stage volatile additions from crustal contamination may thus provide a trigger for explosive eruptions independently of conventional magmatic processes.
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| 10. |
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