Effect of genetically predicted sclerostin on cardiovascular biomarkers, risk factors, and disease outcomes.

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 coron

SUBMITTER: Alcalde-Herraiz M 

PROVIDER: S-EPMC11561231 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature