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Lowering of Circula...
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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Zheng, Jie (author)
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Wheeler, Eleanor (author)
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Pietzner, Maik (author)
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Andlauer, Till F M (author)
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Yau, Michelle S (author)
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Hartley, April E (author)
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Brumpton, Ben Michael (author)
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Rasheed, Humaira (author)
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Kemp, John P (author)
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Frysz, Monika (author)
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Robinson, Jamie (author)
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Reppe, Sjur (author)
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Prijatelj, Vid (author)
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Gautvik, Kaare M (author)
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Falk, Louise (author)
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Maerz, Winfried (author)
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Gergei, Ingrid (author)
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Peyser, Patricia A (author)
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Kavousi, Maryam (author)
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de Vries, Paul S (author)
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Miller, Clint L (author)
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Bos, Maxime (author)
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van der Laan, Sander W (author)
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Malhotra, Rajeev (author)
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Herrmann, Markus (author)
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Scharnagl, Hubert (author)
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Kleber, Marcus (author)
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Dedoussis, George (author)
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Zeggini, Eleftheria (author)
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- Nethander, Maria, 1980 (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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- Ohlsson, Claes, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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- Lorentzon, Mattias, 1970 (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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Wareham, Nick (author)
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Langenberg, Claudia (author)
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Holmes, Michael V (author)
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Davey Smith, George (author)
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Tobias, Jonathan H (author)
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Arthritis & rheumatology (Hoboken, N.J.). - 2326-5205. ; 75:10, s. 1781-1792
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Abstract
Subject headings
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- 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.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.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.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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Humans
- Genome-Wide Association Study
- Diabetes Mellitus
- Type 2
- genetics
- Mendelian Randomization Analysis
- Atherosclerosis
- genetics
- complications
- Myocardial Infarction
- etiology
- Risk Factors
- Hypertension
- Polymorphism
- Single Nucleotide
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Zheng, Jie
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Wheeler, Eleanor
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Pietzner, Maik
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Andlauer, Till F ...
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Yau, Michelle S
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Hartley, April E
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show more...
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Brumpton, Ben Mi ...
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Rasheed, Humaira
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Kemp, John P
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Frysz, Monika
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Robinson, Jamie
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Reppe, Sjur
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Prijatelj, Vid
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Gautvik, Kaare M
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Falk, Louise
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Maerz, Winfried
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Gergei, Ingrid
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Peyser, Patricia ...
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Kavousi, Maryam
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de Vries, Paul S
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Miller, Clint L
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Bos, Maxime
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van der Laan, Sa ...
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Malhotra, Rajeev
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Herrmann, Markus
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Scharnagl, Huber ...
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Kleber, Marcus
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Dedoussis, Georg ...
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Zeggini, Elefthe ...
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Nethander, Maria ...
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Ohlsson, Claes, ...
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Lorentzon, Matti ...
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Wareham, Nick
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Langenberg, Clau ...
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Holmes, Michael ...
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Davey Smith, Geo ...
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Tobias, Jonathan ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Arthritis & rheu ...
- By the university
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University of Gothenburg