| 1. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 2. |
- Seifert, Mariam B., et al.
(författare)
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Genetic variants on chromosomes 7p31 and 12p12 are associated with abnormal atrial electrical activation in patients with early-onset lone atrial fibrillation
- 2019
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Ingår i: Annals of Noninvasive Electrocardiology. - : Wiley. - 1082-720X .- 1542-474X. ; 24:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Abnormal P-wave morphology (PWM) has been associated with a history of atrial fibrillation (AF) in earlier studies. Although lone AF is believed to have substantial genetic basis, studies on associations between single nucleotide polymorphisms (SNP) linked to lone AF and PWM have not been reported. We aimed to assess whether SNPs previously associated with lone AF (rs2200733, rs13376333, rs3807989, and rs11047543) are also linked to P-wave abnormalities. Methods: Four SNPs were studied in 176 unrelated individuals with early-onset lone AF (age at onset <50 years), median age 38 years (19–63 years), 149 men. Using sinus rhythm ECG, orthogonal PWM was classified as Type 1—positive in leads X and Y and negative in lead Z, Type 2—positive in leads X and Y and biphasic (−/+) in lead Z, Type 3—positive in lead X and biphasic in lead Y (+/−), and the remaining as atypical. Results: Two SNPs were found to be significantly associated with altered P-wave morphology distribution: rs3807989 near the gene CAV1/CAV2 and rs11047543 near the gene SOX5. Both SNPs were associated with a higher risk of non-Type 1 P-wave morphology (rs3807989: OR = 4.8, 95% CI = 2.3–10.2, p < 0.001; rs11047543: OR = 4.7, 95% CI = 1.1–20.5, p = 0.04). No association was observed for rs2200733 and rs13376333. Conclusion: In this study, the two variants rs3807989 and rs11047543, previously associated with PR interval and lone AF, were associated with altered P-wave morphology distribution in patients with early-onset lone AF. These findings suggest that common genetic variants may modify atrial conduction properties.
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| 3. |
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| 4. |
- Skov, Morten W., et al.
(författare)
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Risk prediction of atrial fibrillation based on electrocardiographic interatrial block
- 2018
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:11
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Tidskriftsartikel (refereegranskat)abstract
- Background--The electrocardiographic interatrial block (IAB) has been associated with atrial fibrillation (AF). We aimed to test whether IAB can improve risk prediction of AF for the individual person. Methods and Results--Digital ECGs of 152 759 primary care patients aged 50 to 90 years were collected from 2001 to 2011. We identified individuals with P-wave ≥120 ms and the presence of none, 1, 2, or 3 biphasic P-waves in inferior leads. Data on comorbidity, medication, and outcomes were obtained from nationwide registries. We observed a dose-response relationship between the number of biphasic P-waves in inferior leads and the hazard of AF during follow-up. Discrimination of the 10-year outcome of AF, measured by time-dependent area under the curve, was increased by 1.09% (95% confidence interval 0.43-1.74%) for individuals with cardiovascular disease at baseline (CVD) and 1.01% (95% confidence interval 0.40-1.62%) for individuals without CVD, when IAB was added to a conventional risk model for AF. The highest effect of IAB on the absolute risk of AF was observed in individuals aged 60 to 70 years with CVD. In this subgroup, the 10-year risk of AF was 50% in those with advanced IAB compared with 10% in those with a normal P-wave. In general, individuals with advanced IAB and no CVD had a higher risk of AF than patients with CVD and no IAB. Conclusions--IAB improves risk prediction of AF when added to a conventional risk model. Clinicians may consider monitoring patients with IAB more closely for the occurrence of AF, especially for high-risk subgroups.
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| 5. |
- Kurvers, Ralf H. J. M., et al.
(författare)
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The Evolution of Lateralization in Group Hunting Sailfish
- 2017
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 27:4, s. 521-526
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Tidskriftsartikel (refereegranskat)abstract
- Lateralization is widespread throughout the animal kingdom [1-7] and can increase task efficiency via shortening reaction times and saving on neural tissue [8-16]. However, lateralization might be costly because it increases predictability [17-21]. In predator-prey interactions, for example, predators might increase capture success because of specialization in a lateralized attack, but at the cost of increased predictability to their prey, constraining the evolution of lateralization. One unexplored mechanism for evading such costs is group hunting: this would allow individual-level specialization, while still allowing for group-level unpredictability. We investigated this mechanism in group hunting sailfish, Istiophorus platypterus, attacking schooling sardines, Sardinella aurita. During these attacks, sailfish alternate in attacking the prey using their elongated bills to slash or tap the prey [22-24]. This rapid bill movement is either leftward or rightward. Using behavioral observations of identifiable individual sailfish hunting in groups, we provide evidence for individual-level attack lateralization in sailfish. More strongly lateralized individuals had a higher capture success. Further evidence of lateralization comes from morphological analyses of sailfish bills that show strong evidence of one-sided micro-teeth abrasions. Finally, we show that attacks by single sailfish are indeed highly predictable, but predictability rapidly declines with increasing group size because of a lack of population-level lateralization. Our results present a novel benefit of group hunting: by alternating attacks, individual-level attack lateralization can evolve, without the negative consequences of individual-level predictability. More generally, our results suggest that group hunting in predators might provide more suitable conditions for the evolution of strategy diversity compared to solitary life.
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| 6. |
- Marras, Stefano, et al.
(författare)
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Not So Fast : Swimming Behavior of Sailfish during Predator-Prey Interactions using High-Speed Video and Accelerometry
- 2015
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Ingår i: Integrative and Comparative Biology. - : Oxford University Press (OUP). - 1540-7063 .- 1557-7023. ; 55:4, s. 719-727
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Tidskriftsartikel (refereegranskat)abstract
- Synopsis Billfishes are considered among the fastest swimmers in the oceans. Despite early estimates of extremely high speeds, more recent work showed that these predators (e.g., blue marlin) spend most of their time swimming slowly, rarely exceeding 2 m s(-1). Predator-prey interactions provide a context within which one may expect maximal speeds both by predators and prey. Beyond speed, however, an important component determining the outcome of predator-prey encounters is unsteady swimming (i.e., turning and accelerating). Although large predators are faster than their small prey, the latter show higher performance in unsteady swimming. To contrast the evading behaviors of their highly maneuverable prey, sailfish and other large aquatic predators possess morphological adaptations, such as elongated bills, which can be moved more rapidly than the whole body itself, facilitating capture of the prey. Therefore, it is an open question whether such supposedly very fast swimmers do use high-speed bursts when feeding on evasive prey, in addition to using their bill for slashing prey. Here, we measured the swimming behavior of sailfish by using high-frequency accelerometry and high-speed video observations during predator-prey interactions. These measurements allowed analyses of tail beat frequencies to estimate swimming speeds. Our results suggest that sailfish burst at speeds of about 7 m s(-1) and do not exceed swimming speeds of 10 m s(-1) during predator-prey interactions. These speeds are much lower than previous estimates. In addition, the oscillations of the bill during swimming with, and without, extension of the dorsal fin (i.e., the sail) were measured. We suggest that extension of the dorsal fin may allow sailfish to improve the control of the bill and minimize its yaw, hence preventing disturbance of the prey. Therefore, sailfish, like other large predators, may rely mainly on accuracy of movement and the use of the extensions of their bodies, rather than resorting to top speeds when hunting evasive prey.
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| 7. |
- Nielsen, Jonas B., et al.
(författare)
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Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 102:1, s. 103-115
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 × 10−18) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 × 10−11) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.
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| 8. |
- Svendsen, John Inge, et al.
(författare)
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Glacial and environmental changes over the last 60000years in the Polar Ural Mountains, Arctic Russia, inferred from a high-resolution lake record and other observations from adjacent areas
- 2019
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Ingår i: Boreas. - : Wiley. - 0300-9483 .- 1502-3885. ; 48:2, s. 407-431
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge about the glaciation history in the Russian Arctic has to a large extent been based on geomorphological mapping supplemented by studies of short stratigraphical sequences found in exposed sections. Here we present new geochronological data from the Polar Ural Mountains along with a high-resolution sediment record from Bolshoye Shchuchye, the largest and deepest lake in the mountain range. Seismic profiles show that the lake contains a 160-m-thick sequence of unconsolidated lacustrine sediments. A well-dated 24-m-long core from the southern end of the lake spans the last 24cal. ka. From downward extrapolation of sedimentation rates we estimate that sedimentation started about 50-60 ka ago, most likely just after a large glacier had eroded older sediments from the basin. Terrestrial cosmogenic nuclide (TCN) exposure dating (Be-10) of boulders and Optically Stimulated Luminescence (OSL) dating of sediments indicate that this part of the Ural Mountains was last covered by a coherent ice-field complex during Marine Isotope Stage (MIS) 4. A regrowth of the glaciers took place during a late stage of MIS 3, but the central valleys remained ice free until the present. The presence of small- and medium-sized glaciers during MIS 2 is reflected by a sequence of glacial varves and a high sedimentation rate in the lake basin and likewise from Be-10 dating of glacial boulders. The maximum extent of the mountain glaciers during MIS 2 was attained prior to 24cal. ka BP. Some small present-day glaciers, which are now disappearing completely due to climate warming, were only slightly larger during the Last Glacial Maximum (LGM) as compared to AD 1953. A marked decrease in sedimentation rate around 18-17cal. ka BP indicates that the glaciers then became smaller and probably disappeared altogether around 15-14cal. ka BP.
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