Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics

Author:

Bovijn Jonas12ORCID,Krebs Kristi3ORCID,Chen Chia-Yen456ORCID,Boxall Ruth78,Censin Jenny C.12ORCID,Ferreira Teresa1ORCID,Pulit Sara L.1910ORCID,Glastonbury Craig A.1ORCID,Laber Samantha12,Millwood Iona Y.78,Lin Kuang7,Li Liming11,Chen Zhengming7,Milani Lili3ORCID,Smith George Davey1213ORCID,Walters Robin G.78ORCID,Mägi Reedik3,Neale Benjamin M.46ORCID,Lindgren Cecilia M.12914ORCID,Holmes Michael V.17814ORCID

Affiliation:

1. Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, UK.

2. Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.

3. Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.

4. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.

5. Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.

6. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

7. Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.

8. Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.

9. Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.

10. Department of Genetics, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands.

11. Department of Epidemiology and Biostatistics, Peking University Health Science Centre, Peking University, Beijing 100191, China.

12. Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK.

13. Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol BS8 2BN, UK.

14. National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford OX3 9DU, UK.

Abstract

SOST variants that mimic therapeutic inhibition of sclerostin for osteoporosis are associated with higher risk of cardiovascular disease.

Funder

National Institutes of Health

Li Ka Shing Foundation

Wellcome

Medical Research Council

British Heart Foundation

Estonian Research Council

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

John Fell Fund, University of Oxford

NIHR Oxford Biomedical Research Centre

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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