Supplementary Materials

This PDF file includes:

  • Fig. S1. Overview of genetic analysis.
  • Fig. S2. Meta-analysis of romosozumab and risk of cardiovascular events from phase 3 RCTs.
  • Fig. S3. SOST expression is highest in arterial tissues.
  • Fig. S4. SOST mRNA expression by rs7209826 and rs188810925 genotypes.
  • Fig. S5. Colocalization of SOST mRNA expression in tibial artery tissue and eBMD.
  • Fig. S6. Per-allele associations of rs7209826 and rs188810925 with BMD.
  • Fig. S7. Scaled meta-analysis associations of SOST variants with osteoporosis and fracture.
  • Fig. S8. Scaled meta-analysis associations of SOST variants with fracture in the preceding 5 years, at different anatomical sites, in UKBB.
  • Fig. S9. Scaled meta-analysis associations of SOST variants with MI and/or coronary revascularization, CHD, and MACE.
  • Fig. S10. Scaled meta-analysis associations of SOST variants with 11 cardiometabolic outcomes.
  • Fig. S11. Scaled meta-analysis associations of SOST variants with SBP and DBP.
  • Fig. S12. Scaled meta-analysis associations of SOST variants with WHRadjBMI, BMI, LDL and HDL cholesterol, and triglycerides.
  • Fig. S13. Scaled meta-analysis associations of SOST variants with glomerular filtration rate.
  • Fig. S14. SOST variants and various BMD measures.
  • Fig. S15. Associations of different SOST variants with major outcomes of interest.
  • Fig. S16. Phenome-wide association analysis of SOST variants with 1074 binary outcomes in UKBB.
  • Fig. S17. Meta-analysis of romosozumab and risk of clinical fracture from phase 3 RCTs.
  • Fig. S18. Association of SOST instrument and eBMD-associated SNPs with T2D and CHD.
  • Fig. S19. Per-allele association of rs7209826 with eBMD in UKBB and CKB.
  • Fig. S20. Regional association plot of SOST locus in GWAS of eBMD in CKB.
  • Fig. S21. Regional association plots of SOST locus in GWAS of eBMD in UKBB.
  • Fig. S22. Per-allele associations of rs7209826 and selected proxy (rs7220711; r2 = 0.99) with BMD measures.
  • Fig. S23. PRISMA flow diagram.
  • Fig. S24. Assessment of risk of bias in phase 3 RCTs of romosozumab included in meta-analysis.
  • Table S1. Published phase 3 RCTs of romosozumab.
  • Table S2. Reported cardiovascular outcomes at 12 months from published phase 3 RCTs of romosozumab.
  • Table S3. Summary statistics of meta-analyses of cardiovascular events in RCTs of romosozumab.
  • Table S4. Effect of rs7209826 and rs188810925 on SOST gene expression in arterial tissues.
  • Table S5. Colocalization analysis of SOST mRNA expression in tissues and eBMD.
  • Table S6. Scaled estimates for glycemic traits from MAGIC consortium.
  • Table S7. Summary statistics of meta-analyses of scaled allelic estimates.
  • Table S8. Sex-specific summary statistics.
  • Table S9. Colocalization analysis of eBMD with SBP and WHRadjBMI.
  • Table S10. Reported fracture outcomes at 12 months from published phase 3 RCTs of romosozumab.
  • Table S11. Baseline characteristics in UKBB.
  • Table S12. Definitions of outcomes analyzed in UKBB.
  • Table S13. Definitions of outcomes analyzed in PHB.
  • Table S14. Definitions of outcomes analyzed in CKB.
  • Table S15. Per-allele estimates for rs7209826 in CKB.
  • Table S16. GWAS datasets included in present study.
  • Table S17. Search strategy and results for identifying phase 3 RCTs of sclerostin inhibitors.
  • Table S18. Phase 3 RCTs conducted for romosozumab.
  • Table S19. PRISMA checklist for meta-analysis of RCTs.

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