| 11. |
- 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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| 13. |
- Ala-Lahti, Matti, et al.
(författare)
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Transmission of an ICME Sheath Into the Earth's Magnetosheath and the Occurrence of Traveling Foreshocks
- 2021
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 126:12
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Tidskriftsartikel (refereegranskat)abstract
- The transmission of a sheath region driven by an interplanetary coronal mass ejection into the Earth's magnetosheath is studied by investigating in situ magnetic field measurements upstream and downstream of the bow shock during an ICME sheath passage on 15 May 2005. We observe three distinct intervals in the immediate upstream region that included a southward magnetic field component and are traveling foreshocks. These traveling foreshocks were observed in the quasi-parallel bow shock that hosted backstreaming ions and magnetic fluctuations at ultralow frequencies. The intervals constituting traveling foreshocks in the upstream survive transmission to the Earth's magnetosheath, where their magnetic field, and particularly the southward component, was significantly amplified. Our results further suggest that the magnetic field fluctuations embedded in an ICME sheath may survive the transmission if their frequency is below ∼0.01 Hz. Although one of the identified intervals was coherent, extending across the ICME sheath and being long-lived, predicting ICME sheath magnetic fields that may transmit to the Earth's magnetosheath from the upstream at L1 observations has ambiguity. This can result from the strong spatial variability of the ICME sheath fields in the longitudinal direction, or alternatively from the ICME sheath fields developing substantially within the short time it takes the plasma to propagate from L1 to the bow shock. This study demonstrates the complex interplay ICME sheaths have with the Earth's magnetosphere when passing by the planet.
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| 16. |
- Crawford, A. A., et al.
(författare)
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Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease
- 2021
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Ingår i: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 66:6, s. 625-636
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Tidskriftsartikel (refereegranskat)abstract
- The stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from similar to 2.2 M to similar to 7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and alpha 1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06-0.59) and myocardial infarction (0.21, 95% CI 0.00-0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.
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| 17. |
- Jaunsen, Andreas O., et al.
(författare)
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Nordic FAIR Data Collaboration Opportunities
- 2021
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Rapport (refereegranskat)abstract
- Executive summaryIn September 2020 the NeIC Director and board initiated a working group on FAIR collaborationopportunities in the Nordics. This came in the wake of the data tsunami era and the realisationthat machine learning and connected data will become of crucial importance to society andscience. Furthermore, the findings of the EOSC-Nordic project show that the FAIR uptake in theregion is slow and a majority of data repositories are not FAIR, while only a small fractionmeasures up to the available FAIR metrics. Sharing publicly-funded data in a meaningful,reusable way must become part of the normative behaviour in order to nurture data-drivensciences. By enabling data capabilities we are facilitating interdisciplinary data reuse, along withinformation and knowledge exchange. A key objective is data integration, where concepts andproperties, and the relationships between them are linked, forming knowledge graphs andproviding an opportunity to provide insight (new knowledge) from the multitude of relations andpatterns.Although FAIR awareness is growing and there is an appreciation of the Open Science visionamong researchers and support staff, a small survey conducted by the working group confirmssome challenges that are contradictory to the Open Science (OS) movement and contribute toconfusion and status quo when it comes to implementing FAIR. If we are serious aboutembracing OS and the implementation of the FAIR principles it is necessary to ensure that allelements pull in the same direction (this includes infrastructure, skills and services to policiesand incentives). Data stewardship is gradually becoming part of the researcher workflow insome organisations, institutions and departments. Professionalising this crucial support is key tosucceeding in a swift and effective transition to sharing discoverable, accessible and reusabledata. The working group finds that coordinating tasks such as raising awareness, training andskills development and developing common tools and services for research data management(RDM) can contribute to strengthen the momentum of FAIR uptake and better utilise resources,skills and tools across the Nordics. A Nordic coordination office may be one way to orchestratea common strategy on working towards the realisation of the Open Science vision.
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