dc.contributor.author | Zheng, Jie | |
dc.contributor.author | Wheeler, Eleanor | |
dc.contributor.author | Pietzner, Maik | |
dc.contributor.author | Andlauer, Till F.M. | |
dc.contributor.author | Yau, Michelle S. | |
dc.contributor.author | Hartley, April E. | |
dc.contributor.author | Brumpton, Ben Michael | |
dc.contributor.author | Rasheed, Humaira | |
dc.contributor.author | Kemp, John P. | |
dc.contributor.author | Frysz, Monika | |
dc.contributor.author | Robinson, Jamie | |
dc.contributor.author | Reppe, Sjur | |
dc.contributor.author | Prijatelj, Vid | |
dc.contributor.author | Gautvik, Kaare M | |
dc.contributor.author | Falk, Louise | |
dc.contributor.author | Maerz, Winfried | |
dc.contributor.author | Gergei, Ingrid | |
dc.contributor.author | Peyser, Patricia A | |
dc.contributor.author | Kavousi, Maryam | |
dc.contributor.author | de Vries, Paul S. | |
dc.contributor.author | Miller, Clint L. | |
dc.contributor.author | Bos, Maxime | |
dc.contributor.author | Van Der Laan, Sander W. | |
dc.contributor.author | Malhotra, Rajeev | |
dc.contributor.author | Herrmann, Markus | |
dc.contributor.author | Scharnagl, Hubert | |
dc.contributor.author | Kleber, Marcus | |
dc.contributor.author | Dedoussis, George | |
dc.contributor.author | Zeggini, Eleftheria | |
dc.contributor.author | Nethander, Maria | |
dc.contributor.author | Ohlsson, Claes | |
dc.contributor.author | Lorentzon, Mattias | |
dc.contributor.author | Wareham, Nick | |
dc.contributor.author | Langenberg, Claudia | |
dc.contributor.author | Holmes, Michael V. | |
dc.contributor.author | Smith, George Davey | |
dc.contributor.author | Tobias, Jonathan H. | |
dc.date.accessioned | 2024-01-30T12:54:47Z | |
dc.date.available | 2024-01-30T12:54:47Z | |
dc.date.created | 2023-06-05T13:43:59Z | |
dc.date.issued | 2023 | |
dc.identifier.issn | 2326-5191 | |
dc.identifier.uri | https://hdl.handle.net/11250/3114507 | |
dc.description.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. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Wiley | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | 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 | en_US |
dc.title.alternative | 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 | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.subject.nsi | VDP::Medisinsk molekylærbiologi: 711 | en_US |
dc.subject.nsi | VDP::Medical molecular biology: 711 | en_US |
dc.subject.nsi | VDP::Medisinsk molekylærbiologi: 711 | en_US |
dc.subject.nsi | VDP::Medical molecular biology: 711 | en_US |
dc.subject.nsi | VDP::Medisinsk molekylærbiologi: 711 | en_US |
dc.subject.nsi | VDP::Medical molecular biology: 711 | en_US |
dc.subject.nsi | VDP::Medisinsk molekylærbiologi: 711 | en_US |
dc.subject.nsi | VDP::Medical molecular biology: 711 | en_US |
dc.source.journal | Arthritis & Rheumatology | en_US |
dc.identifier.doi | 10.1002/art.42538 | |
dc.identifier.cristin | 2151902 | |
dc.relation.project | Lovisenberg Diakonale Sykehus: Legat til forskning | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |