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| Verfasst von: | Zheng, Jie [VerfasserIn]  |
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| | Wheeler, Eleanor [VerfasserIn] |
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| | Pietzner, Maik [VerfasserIn] |
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| | Andlauer, Till F. M. [VerfasserIn] |
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| | Yau, Michelle S. [VerfasserIn] |
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| | Hartley, April E. [VerfasserIn] |
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| | Brumpton, Ben Michael [VerfasserIn] |
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| | Rasheed, Humaira [VerfasserIn] |
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| | Kemp, John P. [VerfasserIn] |
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| | Frysz, Monika [VerfasserIn] |
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| | Robinson, Jamie [VerfasserIn] |
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| | Reppe, Sjur [VerfasserIn] |
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| | Prijatelj, Vid [VerfasserIn] |
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| | Gautvik, Kaare M. [VerfasserIn] |
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| | Falk, Louise [VerfasserIn] |
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| | März, Winfried [VerfasserIn] |
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| | Gergei, Ingrid [VerfasserIn] |
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| | Peyser, Patricia A. [VerfasserIn] |
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| | Kavousi, Maryam [VerfasserIn] |
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| | Vries, Paul S. de [VerfasserIn] |
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| | Miller, Clint L. [VerfasserIn] |
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| | Bos, Maxime [VerfasserIn] |
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| | van der Laan, Sander W. [VerfasserIn] |
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| | Malhotra, Rajeev [VerfasserIn] |
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| | Herrmann, Markus [VerfasserIn] |
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| | Scharnagl, Hubert [VerfasserIn] |
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| | Kleber, Marcus E. [VerfasserIn] |
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| | Dedoussis, George [VerfasserIn] |
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| | Zeggini, Eleftheria [VerfasserIn] |
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| | Nethander, Maria [VerfasserIn] |
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| | Ohlsson, Claes [VerfasserIn] |
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| | Lorentzon, Mattias [VerfasserIn] |
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| | Wareham, Nick [VerfasserIn] |
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| | Langenberg, Claudia [VerfasserIn] |
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| | Holmes, Michael V. [VerfasserIn] |
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| | Davey Smith, George [VerfasserIn] |
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| | Tobias, Jonathan H. [VerfasserIn] |
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| Titel: | Lowering of circulating sclerostin may increase risk of atherosclerosis and its risk factors |
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| Titelzusatz: | evidence from a genome-wide association meta-analysis followed by mendelian randomization |
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| Verf.angabe: | Jie Zheng, Eleanor Wheeler, Maik Pietzner, Till FM Andlauer, Michelle S Yau, April E Hartley, Ben Michael Brumpton, Humaira Rasheed, John P Kemp, Monika Frysz, Jamie Robinson, Sjur Reppe, Vid Prijatelj, Kaare M Gautvik, Louise Falk, Winfried Maerz, Ingrid Gergei, Patricia A Peyser, Maryam Kavousi, Paul S de Vries, Clint L Miller, Maxime Bos, Sander W van der Laan, Rajeev Malhotra, Markus Herrmann, Hubert Scharnagl, Marcus Kleber, George Dedoussis, Eleftheria Zeggini, Maria Nethander, Claes Ohlsson, Mattias Lorentzon, Nick Wareham, Claudia Langenberg, Michael V Holmes, George Davey Smith, and Jonathan H Tobias |
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| E-Jahr: | 2023 |
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| Jahr: | October 2023 |
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| Umfang: | 12 S. |
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| Fussnoten: | Online veröffentlicht: 25. April 2023 ; Gesehen am 07.02.2024 |
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| Titel Quelle: | Enthalten in: Arthritis & rheumatology |
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| Ort Quelle: | Hoboken, NJ : Wiley, 2014 |
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| Jahr Quelle: | 2023 |
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| Band/Heft Quelle: | 75(2023), 10 vom: Okt., Seite 1781-1792 |
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| ISSN Quelle: | 2326-5205 |
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| Abstract: | Objective In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors. Methods A genome-wide association study meta-analysis was performed of circulating sclerostin levels in 33,961 European individuals. Mendelian randomization (MR) was used to predict the causal effects of sclerostin lowering on 15 atherosclerosis-related diseases and risk factors. Results We found that 18 conditionally independent variants were associated with circulating sclerostin. Of these, 1 cis signal in SOST and 3 trans signals in B4GALNT3, RIN3, and SERPINA1 regions showed directionally opposite signals for sclerostin levels and estimated bone mineral density. Variants with these 4 regions were selected as genetic instruments. MR using 5 correlated cis-SNPs suggested that lower sclerostin increased the risk of type 2 diabetes mellitus (DM) (odds ratio [OR] 1.32 [95% confidence interval (95% CI) 1.03-1.69]) and myocardial infarction (MI) (OR 1.35 [95% CI 1.01-1.79]); sclerostin lowering was also suggested to increase the extent of coronary artery calcification (CAC) (β = 0.24 [95% CI 0.02-0.45]). MR using both cis and trans instruments suggested that lower sclerostin increased hypertension risk (OR 1.09 [95% CI 1.04-1.15]), but otherwise had attenuated effects. Conclusion This study provides genetic evidence to suggest that lower levels of sclerostin may increase the risk of hypertension, type 2 DM, MI, and the extent of CAC. Taken together, these findings underscore the requirement for strategies to mitigate potential adverse effects of romosozumab treatment on atherosclerosis and its related risk factors. |
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| DOI: | doi:10.1002/art.42538 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1002/art.42538 |
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| | kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/art.42538 |
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| | DOI: https://doi.org/10.1002/art.42538 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1880185490 |
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| Verknüpfungen: | → Zeitschrift |
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Lowering of circulating sclerostin may increase risk of atherosclerosis and its risk factors / Zheng, Jie [VerfasserIn]; October 2023 (Online-Ressource)
