| 1. |
- Evangelou, Evangelos, et al.
(författare)
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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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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)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. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 4. |
- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 6. |
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Transforming Warriors : The ritual organisation of military force
- 2016
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- This volume offers an interdisciplinary study of how different cultures have sought to transform individuals into warriors. War changes people, however a less explored question is how different societies want people to change as they are turned into warriors. When societies go to war they recognize that a boundary is being crossed. The participants are expected to do things that are otherwise prohibited, or at least governed by different rules. This edited volume analyses how different cultures have conceptualized the transformations of an individual passing from a peacetime to a wartime existence to become an active warrior. Despite their differences, all societies grapple with the same question: how much of the individual's peace-self should be and can be retained in the state of war? The book explores cases such as the Nordic berserkers, the Japanese samurai, and European knights, as well as modern soldiers in Germany, Liberia, and Sweden. It shows that archaic and modern societies are more similar than we usually think: both kinds of societies use myths, symbols, and rituals to create warriors. Thus, this volume seeks to redefine theories of modernization and secularization. It shows that military organizations need to take myths, symbols, and rituals seriously in order to create effective units. This book will be of much interest to students of military studies, war studies, sociology, religion, and international relations in general.
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| 7. |
- Broadaway, K Alaine, et al.
(författare)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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| 8. |
- Jackson, Peter, 1971-
(författare)
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A guest at the table of the gods : Religion and the origins of academic life
- 2015
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Ingår i: Temenos. - : Temenos. - 0497-1817 .- 2342-7256. ; 51:2, s. 257-276
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Tidskriftsartikel (refereegranskat)abstract
- Proceeding from the Renaissance philosopher Giovanni Pico della Mirandola's Oration on the Dignity of Man, this paper is an attempt to survey the historical premises of the academic study of religion, both as a practice of detaching the subject matter of religion from its institutional restrictions, and as a practice of rehearsing certain modalities of thought and action (philosophical as well as religious) flourishing in the ancient world long before Christianity conquered the sphere of public worship in the fourth century. By paying particular attention to themes of suspension and commensality in religious practice and discourse, an attempt is made to reconsider the critical task of the history of religions, famously devised by Bruce Lincoln as a reversal of the orientation of religious discourse.
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| 9. |
- Jackson, Peter, 1971-
(författare)
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A New Order of the Ages : Eschatological Vision in Virgil and Beyond
- 2012
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Ingår i: Numen. - : Brill. - 0029-5973 .- 1568-5276. ; 59:5-6, s. 533-544
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Tidskriftsartikel (refereegranskat)abstract
- Proceeding from the Latin mottoes for the Great Seal of the United States, this paper explores the use and repercussions of eschatological themes in Virgil’s poetry. A hith-herto unnoticed datum in the history of the Great Seal’s final design exemplifies how comparatively recent readings of the myth of Aeneas and the Cumaean Sibyl could inform our understanding of how the same myth was conceived in the Augustan Age. The discussion revolves around topics such as ekphrasis, the conflation of memoir and myth, and the eschatological significance of spatial and temporal transmission. The final part of the paper introduces some new thoughts concerning the ludi tarentini and the centennial life span.
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| 10. |
- Jackson, Peter, 1971-
(författare)
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A Song Worth Fifty Cows : Graeco-Indo-Iranian Variations on the Etiology of Sacrifice
- 2014
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Ingår i: Münchener Studien zur Sprachwissenschaft. - München. - 0077-1910. ; 68:1, s. 101-118
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Tidskriftsartikel (refereegranskat)abstract
- This paper explores how the social reality of an ancient sacrificial economy backlights through the medium of mythical etiology, even in contexts where this reality seems to have lost its direct impact. By comparing crucial moments in the Greek myth of Hermes’ theft of Apollo’s cattle (first rendered at length in the Homeric Hymn to Hermes) with Indo-Iranian reflexes of the so-called Vala-myth, an attempt is made to resolve a few perplexities evoked by the Greek myth as well as elucidating general aspects of Greek and Indo-European poetics. In addition to these considerations, the original meaning ‘(paid) ally, client’ is proposed for Greek Ὀρφεύς/Vedic R̥bhúḥ.
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