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- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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- Ackley, K., et al.
(författare)
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Observational constraints on the optical and near-infrared emission from the neutron star-black hole binary merger candidate S190814bv
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 643
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Tidskriftsartikel (refereegranskat)abstract
- Context. Gravitational wave (GW) astronomy has rapidly reached maturity, becoming a fundamental observing window for modern astrophysics. The coalescences of a few tens of black hole (BH) binaries have been detected, while the number of events possibly including a neutron star (NS) is still limited to a few. On 2019 August 14, the LIGO and Virgo interferometers detected a high-significance event labelled S190814bv. A preliminary analysis of the GW data suggests that the event was likely due to the merger of a compact binary system formed by a BH and a NS.Aims. In this paper, we present our extensive search campaign aimed at uncovering the potential optical and near infrared electromagnetic counterpart of S190814bv. We found no convincing electromagnetic counterpart in our data. We therefore use our non-detection to place limits on the properties of the putative outflows that could have been produced by the binary during and after the merger.Methods. Thanks to the three-detector observation of S190814bv, and given the characteristics of the signal, the LIGO and Virgo Collaborations delivered a relatively narrow localisation in low latency - a 50% (90%) credible area of 5 deg(2) (23 deg(2)) - despite the relatively large distance of 26752 Mpc. ElectromagNetic counterparts of GRAvitational wave sources at the VEry Large Telescope collaboration members carried out an intensive multi-epoch, multi-instrument observational campaign to identify the possible optical and near infrared counterpart of the event. In addition, the ATLAS, GOTO, GRAWITA-VST, Pan-STARRS, and VINROUGE projects also carried out a search on this event. In this paper, we describe the combined observational campaign of these groups.Results. Our observations allow us to place limits on the presence of any counterpart and discuss the implications for the kilonova (KN), which was possibly generated by this NS-BH merger, and for the strategy of future searches. The typical depth of our wide-field observations, which cover most of the projected sky localisation probability (up to 99.8%, depending on the night and filter considered), is r similar to 22 (resp. K similar to 21) in the optical (resp. near infrared). We reach deeper limits in a subset of our galaxy-targeted observations, which cover a total similar to 50% of the galaxy-mass-weighted localisation probability. Altogether, our observations allow us to exclude a KN with large ejecta mass M greater than or similar to 0.1 M-circle dot to a high (> 90%) confidence, and we can exclude much smaller masses in a sub-sample of our observations. This disfavours the tidal disruption of the neutron star during the merger.Conclusions. Despite the sensitive instruments involved in the campaign, given the distance of S190814bv, we could not reach sufficiently deep limits to constrain a KN comparable in luminosity to AT 2017gfo on a large fraction of the localisation probability. This suggests that future (likely common) events at a few hundred megaparsecs will be detected only by large facilities with both a high sensitivity and large field of view. Galaxy-targeted observations can reach the needed depth over a relevant portion of the localisation probability with a smaller investment of resources, but the number of galaxies to be targeted in order to get a fairly complete coverage is large, even in the case of a localisation as good as that of this event.
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| 7. |
- 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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