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Zheng, Jie
[VerfasserIn];
Wheeler, Eleanor
[VerfasserIn];
Pietzner, Maik
[VerfasserIn];
Andlauer, Till F. M.
[VerfasserIn];
Yau, Michelle S.
[VerfasserIn];
Hartley, April E.
[VerfasserIn];
Brumpton, Ben Michael
[VerfasserIn];
Rasheed, Humaira
[VerfasserIn];
Kemp, John P.
[VerfasserIn];
Frysz, Monika
[VerfasserIn];
Robinson, Jamie
[VerfasserIn];
Reppe, Sjur
[VerfasserIn];
Prijatelj, Vid
[VerfasserIn];
Gautvik, Kaare M.
[VerfasserIn];
Falk, Louise
[VerfasserIn];
März, Winfried
[VerfasserIn];
Gergei, Ingrid
[VerfasserIn];
Peyser, Patricia A.
[VerfasserIn];
Kavousi, Maryam
[VerfasserIn];
Vries, Paul S. de
[VerfasserIn];
Miller, Clint L.
[VerfasserIn];
Bos, Maxime
[VerfasserIn];
van der Laan, Sander W.
[VerfasserIn];
Malhotra, Rajeev
[VerfasserIn];
[...]
Lowering of circulating sclerostin may increase risk of atherosclerosis and its risk factors
: evidence from a genome-wide association meta-analysis followed by mendelian randomization
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- Medientyp: E-Artikel
- Titel: Lowering of circulating sclerostin may increase risk of atherosclerosis and its risk factors : evidence from a genome-wide association meta-analysis followed by mendelian randomization
- Beteiligte: Zheng, Jie [VerfasserIn]; Wheeler, Eleanor [VerfasserIn]; Pietzner, Maik [VerfasserIn]; Andlauer, Till F. M. [VerfasserIn]; Yau, Michelle S. [VerfasserIn]; Hartley, April E. [VerfasserIn]; Brumpton, Ben Michael [VerfasserIn]; Rasheed, Humaira [VerfasserIn]; Kemp, John P. [VerfasserIn]; Frysz, Monika [VerfasserIn]; Robinson, Jamie [VerfasserIn]; Reppe, Sjur [VerfasserIn]; Prijatelj, Vid [VerfasserIn]; Gautvik, Kaare M. [VerfasserIn]; Falk, Louise [VerfasserIn]; März, Winfried [VerfasserIn]; Gergei, Ingrid [VerfasserIn]; Peyser, Patricia A. [VerfasserIn]; Kavousi, Maryam [VerfasserIn]; Vries, Paul S. de [VerfasserIn]; Miller, Clint L. [VerfasserIn]; Bos, Maxime [VerfasserIn]; van der Laan, Sander W. [VerfasserIn]; Malhotra, Rajeev [VerfasserIn]; Herrmann, Markus [VerfasserIn]; Scharnagl, Hubert [VerfasserIn]; Kleber, Marcus E. [VerfasserIn]; Dedoussis, George [VerfasserIn]; Zeggini, Eleftheria [VerfasserIn]; Nethander, Maria [VerfasserIn]; Ohlsson, Claes [VerfasserIn]; Lorentzon, Mattias [VerfasserIn]; Wareham, Nick [VerfasserIn]; Langenberg, Claudia [VerfasserIn]; Holmes, Michael V. [VerfasserIn]; Davey Smith, George [VerfasserIn]; Tobias, Jonathan H. [VerfasserIn]
- Erschienen: October 2023
- Erschienen in: Arthritis & rheumatology ; 75(2023), 10 vom: Okt., Seite 1781-1792
- Sprache: Englisch
- DOI: 10.1002/art.42538
- ISSN: 2326-5205
- Identifikator:
- Entstehung:
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Anmerkungen:
Online veröffentlicht: 25. April 2023
- Beschreibung: 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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