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- 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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| 2. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 4. |
- Beech, Jason, et al.
(författare)
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Sorting cells by size, shape and deformability
- 2012
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 12, s. 1048-1051
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Tidskriftsartikel (refereegranskat)abstract
- While size has been widely used as a parameter in cellular separations, in this communication we show how shape and deformability, a mainly untapped source of specificity in preparative and analytical microfluidic devices can be measured and used to separate cells. © 2012 The Royal Society of Chemistry.
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| 7. |
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Gränser och oändligheter – Musikalisk och litterär komposition, en forskningsrapport : 'Compositional' Becoming, Complexity, and Critique
- 2020
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- ur Förordet: Det övergripande forskningsprogrammet söker spåra några mindre delar av det vidsträckta landskap av mänskliga och icke-mänskliga betingelser, strategier och komplexiteter som ligger till grund för arbetet inom musikalisk och litterär komposition. Sektion 1 inleds med utdrag ur Tapeshavet av Gunnar D Hansson som är en text kring plats, natur, dikt och poetik, och där de geologiska beskrivningarna även blir en metafor för diktsamlingens egen organisationsprincip. Detta följs av reflektioner kring bakomliggande tankar, vidare gestaltningar, och meta-reflektioner. En del kompositionella frågeställningar tas vidare genom presentationer av och reflektioner kring ett antal musikaliska kompositioner, ljud-installationer och gestaltade konsert-föreställningar. Sektion 2 diskuterar litterära och musikaliska praktiker och skilda verksamma poetiker utifrån bland annat Inger Christensen, Elfride Jelinek, kommissarie Maigret och Bengt-Emil Johnson, samt en avslutande epilog kring symmetribegreppet. From the Preamble: On the whole the project can be said to trace some small parts of the vast landscape of strategies and complexities underlying musical and literary composition. The artistic investigations in different ways take their point of departure in some of the textual, musical, and informational conditions for related artistic work. Would it be possible to expand some of our lived metaphors by looking at these different levels and areas of complexity and time, how they are connected and why we might interpret and inhabit them as we do? Addressing the physical (biological) and cultural complexities we and our artefacts both are made out of, and dynamically move within, and in doing this, in some way, try to “ignore the right details, [...] still preserving the essence of what is complicated” as Carina Curto puts it in an article in Quanta Magazine. But also, through some of the subprojects, in different ways address conventional metonymical concepts and compressions like ‘a poem’, ‘listening’, or ‘a (musical) composition’.
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| 10. |
- Lannering, Birgitta, 1948, et al.
(författare)
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Classification, incidence and survival analyses of children with CNS tumours diagnosed in Sweden 1984-2005.
- 2009
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 98:10, s. 1620-7
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Primary tumours in the central nervous system (CNS) are the second most common malignancy in childhood after leukaemia. Sweden has a high incidence and a high-survival rate in international comparative studies. This has raised the question about the type of tumours included in the Swedish Cancer registry. We therefore compared international data to the Swedish Childhood Cancer registry. METHODS: Central nervous system tumours registered in the Swedish Childhood Cancer Registry were reclassified according to ICCC-3. Incidence and survival analyses were performed in the study population. RESULTS: There were 1479 children (<15 years) in Sweden diagnosed with CNS tumours 1984-2005. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 4.2/100,000 children. The survival rates have not improved significantly between the two time periods before/after 1995 (70% vs. 74%; p = 0.10). CONCLUSIONS: The mean annual incidence of children with CNS tumours was 4.2/100,000 and has not increased during the study period. Survival rate for brain tumours at 10 years follow-up was 72%.
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