Response to comment on "Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics"

Jonas Bovijn^{1

2}, Kristi Krebs³, Chia-Yen Chen^{4

5

6}, Ruth Boxall^{7

8}, Jenny C Censin^{1

2}, Teresa Ferreira¹, Sara L Pulit^{1

9

10}, Craig A Glastonbury¹, Samantha Laber^{1

2}, Iona Y Millwood^{7

8}, Kuang Lin⁷, Liming Li¹¹, Zhengming Chen⁷, Lili Milani³, George Davey Smith^{12

13}, Robin G Walters^{7

8}, Reedik Mägi³, Benjamin M Neale^{4

6}, Cecilia M Lindgren^{1

2

9

14}, Michael V Holmes^{1

7

8

14}

Affiliations

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.

PMID: 34851696
DOI: 10.1126/scitranslmed.abf4530

Comment

Response to comment on "Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics"

Jonas Bovijn et al. Sci Transl Med. 2021 Dec.

. 2021 Dec;13(622):eabf4530.

doi: 10.1126/scitranslmed.abf4530. Epub 2021 Dec 1.

Authors

Affiliations

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.

PMID: 34851696
DOI: 10.1126/scitranslmed.abf4530

Abstract

Triangulation of evidence from clinical trials and human genetics suggests a potential excess risk of cardiovascular disease events arising from therapeutic inhibition of sclerostin.

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Comment on

Macrophage migration inhibitory factor drives pathology in a mouse model of spondyloarthritis and is associated with human disease.
Nakamura A, Zeng F, Nakamura S, Reid KT, Gracey E, Lim M, Leng L, Jo S, Park YS, Kusuda M, Machhar R, Boroojeni SF, Wu B, Rossomacha E, Kim TH, Ciccia F, Rockel JS, Kapoor M, Inman RD, Jurisica I, Crome SQ, Bucala R, Haroon N. Nakamura A, et al. Sci Transl Med. 2021 Oct 20;13(616):eabg1210. doi: 10.1126/scitranslmed.abg1210. Epub 2021 Oct 20. Sci Transl Med. 2021. PMID: 34669443
Comment on "Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics".
Hólm H, Sulem P, Tragante V, Thorsteinsdottir U, Gudbjartsson DF, Stefansson K. Hólm H, et al. Sci Transl Med. 2021 Dec;13(622):eabe8497. doi: 10.1126/scitranslmed.abe8497. Epub 2021 Dec 1. Sci Transl Med. 2021. PMID: 34851692

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Response to comment on "Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics"

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Response to comment on "Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics"

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Abstract

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