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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 by Jie Zheng; Eleanor Wheeler; Maik Pietzner; Till F. M. 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; Jonathan H. Tobias is a Medicine article available to read on EtoBox.

What is 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 about?

## 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 (CA

Who reads 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?

Author

Jie Zheng; Eleanor Wheeler; Maik Pietzner; Till F. M. 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; Jonathan H. Tobias

Publisher

Wiley Periodicals, Inc.

Published

2023

Language

EN

Field

Medicine (Health Sciences)