| Title: |
Effect of genetically predicted sclerostin on cardiovascular biomarkers, risk factors, and disease outcomes |
| Authors: |
Marta Alcalde-Herraiz, JunQing Xie, Danielle Newby, Clara Prats, Dipender Gill, María Gordillo-Marañón, Daniel Prieto-Alhambra, Martí Català, Albert Prats-Uribe |
| Source: |
Nature Communications, Vol 15, Iss 1, Pp 1-12 (2024) |
| Publisher Information: |
Nature Portfolio, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Science |
| Subject Terms: |
Science |
| More Details: |
Abstract Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to estimate the causal effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans and selected 2 SNPs to be used as instruments. We included heel bone mineral density and hip fracture risk as positive control outcomes. Public GWAS and UK Biobank patient-level data were used for the study outcomes, which include cardiovascular events, risk factors, and biomarkers. Lower sclerostin levels were associated with higher bone mineral density and 85% reduction in hip fracture risk. However, genetically predicted lower sclerostin levels led to 25–85% excess coronary artery disease risk, 40% to 60% increased risk of type 2 diabetes, and worse cardiovascular biomarkers values, including higher triglycerides, and decreased HDL cholesterol levels. Results also suggest a potential (but borderline) association with increased risk of myocardial infarction. Our study provides genetic evidence of a causal relationship between reduced levels of sclerostin and improved bone health and fracture protection, but increased risk of cardiovascular events and risk factors. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
https://doaj.org/toc/2041-1723 |
| DOI: |
10.1038/s41467-024-53623-5 |
| Access URL: |
https://doaj.org/article/4350d228ebd54f46aff3945119c4aa78 |
| Accession Number: |
edsdoj.4350d228ebd54f46aff3945119c4aa78 |
| Database: |
Directory of Open Access Journals |
