| 1. |
- Evangelou, Evangelos, et al.
(author)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Journal article (peer-reviewed)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 2. |
- van de Vegte, Yordi, et al.
(author)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 3. |
- Kutscher, Liselott, 1976-
(author)
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Export and sources of organic carbon in the Lena River basin, Northeastern Siberia
- 2016
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Licentiate thesis (other academic/artistic)abstract
- Permafrost areas are considered to be one of the largest terrestrial storages of carbon. In a warming climate these areas are expected to experience changes in carbon transport to rivers and the oceans due to permafrost thawing, which could enhance erosion, change water flow pathways and increase greenhouse gas emissions. Large amounts of the carbon transported from the terrestrial environment to rivers are in the form of natural organic matter (NOM). The Lena River basin in northeastern Siberia, which is mainly underlain by continuous permafrost, is the largest contributor of NOM to the Arctic Ocean. In this study we present a spatial data set of NOM, including concentrations and stable carbon isotope values (δ13C) of dissolved (DOC) and particulate organic carbon (POC) as well as carbon and nitrogen ratios (C/N) from 77 sample stations in the Lena River and its tributaries. The samples were collected during two field seasons in July 2012 and June 2013.The results from this study showed large spatial variations in concentrations, annual export and fluxes of organic carbon. These variations were primarily due to variations in discharge and topography. The δ13C and C/N indicated that terrestrial sources such as plants and soil organic matter (SOM), were the main sources of the dissolved organic matter (DOM), while particulate organic matter (POM) was mainly derived from aquatic produced material or SOM. There were clear differences in δ13C and C/N of DOM between sampling years, indicating more surficial flow pathways in samples collected earlier in the summer compared to samples collected later in the summer. The δ13C of POM was correlated with water temperatures and topography, showing that tributaries with origin in mountainous areas in general had soil derived POM and lower water temperatures, while tributaries from lowland areas had higher water temperatures and more influence of aquatic sources. We suggest that this pattern is probably due to differences in water flow pathways. Shifts in export of NOM from drainage areas underlain by permafrost will likely be dependent of spatial changes in hydroclimate and the depth of the active layer in a warming climate.
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| 4. |
- Domange, Raphaël, 1983-
(author)
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The vowels of Delhi English : Three studies in sociophonetics
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Addressing the dearth of sociolinguistic variation research in the “new” varieties of English (D. Sharma, 2017b), this dissertation consists of a set of three sociophonetic studies on an urban dialect of Indian English. Relying upon community-based methods of data collection, this dissertation examines the vowels of an intergenerational sample of speakers from the upper-middle class neighbourhoods of Delhi. Each study of this compilation is guided by two principal goals. The first one is descriptive, that is to provide a detailed instrumental phonetic characterisation of the phonological vowels that compose the inventory of the variety. The second aim, which is historical, is to shed light of how Indian English carves its own diachronic trajectory, addressing issues relating to, for instance, diachronic stability and the transmission of language change across generations of speakers. Study I thus examines variation in the mid and low back rounded area of the vowel space, and seeks to draw relevant implications from the presence of lexical distributional “archaisms” (Wells, 1982, p. 626) in those vowels. Study II, on the other hand, is concerned with describing a chain-shift-like change in the short front vowels, and discusses the conditions of possibility for such change to occur in a mixed L1-L2 context. Lastly, Study III builds upon a complex allophonic “split” found and summarily described in Study II, and identifies this phenomenon as an element of historical convergence with geographically distant, unrelated, post-colonial varieties of English. Overall, several previously unreported features were found and described in detail in this dissertation, while important clarifications were also brought to areas that have been considered problematic in former descriptive works. Importantly, the studies also demonstrate that the variety under study and its patterns of variation seem to be, in general, amenable to the same kind of empirical analysis as other, so-called “native,” varieties of English, and call into question a number of ordinary assumptions on Indian English.
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| 5. |
- Ntalla, Ioanna, et al.
(author)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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| 6. |
- Natchimuthu, Sivakiruthika
(author)
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Freshwater methane and carbon dioxide fluxes : Spatio-temporal variability and an integrated assessment of lake and stream emissions in a catchment
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Freshwater bodies such as lakes and streams release the greenhouse gases methane (CH4) and carbon dioxide (CO2) into the atmosphere. Global freshwater CH4 and CO2 emissions have been estimated to be of a similar magnitude to the global land or ocean carbon sink, and are thus significant components of global carbon budgets. However, the data supporting global estimates frequently lacks information regarding spatial and temporal variability and are thus highly inaccurate. In this thesis, detailed studies of the spatio-temporal variability of CH4 and CO2 fluxes were conducted in the open water areas of lakes and streams within a whole catchment in Sweden. One aim was also to evaluate the importance of spatio-temporal variability in lake and stream fluxes when making whole catchment aquatic or large scale assessments. Apart from the expected large spatio-temporal variability in lake fluxes, interactions between spatial and temporal variability in CH4 fluxes were found. Shallow lakes and shallow areas of lakes were observed to emit more CH4 as compared to their deeper counterparts. This spatial variability interacted with the temporal variability driven by an exponential temperature response of the fluxes, which meant that shallow waters were more sensitive to warming than deeper ones. Such interactions may be important for climate feedbacks. Surface water CO2 in lakes showed significant spatio-temporal variability and, when considering variability in both space and time, CO2 fluxes were largely controlled by concentrations, rather than gas transfer velocities. Stream fluxes were also highly variable in space and time and in particular, stream CH4 fluxes were surprisingly large and more variable than CO2 fluxes. Fluxes were large from stream areas with steep slopes and periods of high discharge which occupied a small fraction of the total stream area and the total measurement period, respectively, and a failure to account for these spatially distinct or episodic high fluxes could lead to underestimates. The total aquatic fluxes from the whole catchment were estimated by combining the measurements in open waters of lakes and streams. Using our data, recommendations on improved study designs for representative measurements in lakes and streams were provided for future studies. Thus, this thesis presents findings relating to flux regulation in lakes and streams, and urges forthcoming studies to better consider spatio-temporal variability so as to achieve unbiased large-scale estimates.
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| 7. |
- Serikova, Svetlana, 1989-
(author)
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Carbon Emissions from Western Siberian Inland Waters
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Inland waters (i.e. rivers, streams, lakes, ponds) emit carbon (C) into the atmosphere. The magnitude of global inland water C emission has been estimated to equal the global ocean C sink, thus making inland waters an important component of the global C cycle. Yet, the data used in estimating the magnitude of global inland water C emission lacks measurements of inland water C emissions from permafrost-affected regions in general and from Russia in particular, despite permafrost covering ~25% of the Northern Hemisphere and ~65% of Russia. This lack of data questions the accuracy of the current estimate of global inland water C emission and its predictive power in assessing changes in the global C cycle following permafrost thaw.In this thesis, we conducted detailed measurements of river and lake C emissions across ~1000 km permafrost gradient of Western Siberia (from permafrost-free to continuous permafrost zone) and assessed the magnitude of the total C emission from Western Siberian inland waters. We found that river and lake C emissions varied across the permafrost gradient with river C emissions being greatest in areas where permafrost is actively degrading, and lake C emissions being greatest in areas where permafrost is still intact. We also found that river and lake C emissions are likely driven by different factors with river C emissions being mainly controlled by temperature and hydrological conditions, whereas lake C emissions by sediment respiration and availability of recently thawed organic C. Further, we estimated the total C emission from Western Siberian inland waters to be greater than previously thought and exceeding the C export from this region to the Arctic Ocean. Such finding implies that a major part of the terrestrially-derived C is lost in Western Siberian inland waters, making this region a hotspot for inland water C emission following permafrost thaw. We also showed that apart from C emissions measurements across different inland water types and across the landscape, estimates of inland water surface areas are needed for accurate assessments of the total inland water C emission of any given region. Particularly, water surface areas of streams and ponds as well as inundated floodplains, especially in years of extreme flood events, are important for quantifying the total inland water C emission. Overall, this thesis presents new data related to C emissions from rivers and lakes in an area that undergoes rapid permafrost thaw, and urges to account for all inland water types and their respective water surface areas when attempting to achieve unbiased estimates of the inland water contribution to the atmospheric C budget.
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