Genetic Correlation, Shared Loci, and Causal Association Between Sex Hormone-Binding Globulin and Bone Mineral Density: Insights From a Large-Scale Genomewide Cross-Trait Analysis
Authors' conclusion
Our work reveals a shared genetic basis between SHBG and eBMD, substantiated by multiple pleiotropic loci and a robust causal relationship.
Study context
- Population
- GWAS summary statistics for sex hormone-binding globulin (SHBG), BMI-adjusted SHBG (SHBGa, N = 368,929) and heel estimated BMD (estimated bone mineral density (eBMD), N = 426,824)GWAS summary statistics for SHBG 370,125
- Outcome
- Genetic overlap between SHBG and eBMD
Methodological detailsgenetic correlation, cross-trait meta-analysis, colocalization, Mendelian randomization
- Genetic correlation
- Cross-trait meta-analysis
- Colocalization
- Mendelian randomization
Pooled result
As reported in the abstract
- Overall genetic correlation SHBG–eBMD (inverse)
- rg = −0.11, p = 3.34 × 10-10
- Genomic regions with significant local genetic correlation
- 11
- Shared loci in cross-trait meta-analysis
- 219
- Novel shared loci
- seven
- Novel loci shown to colocalize (rs6542680, rs8178616, rs147110934, rs815625)
- four
- MR causal effect of SHBG on eBMD
- beta = −0.22, p = 3.04 × 10-13
Further pooled results
MR causal effect of SHBG on eBMD, men
- Men
- beta = −0.16, p = 1.99 × 10-6
MR causal effect of SHBG on eBMD, women
- Women
- beta = −0.19, p = 2.73 × 10-9
Sensitivity analysis replacing SHBG with SHBGa
- Genetic correlations, pleiotropic loci and causal associations did not change substantially
Original publication
Genetic Correlation, Shared Loci, and Causal Association Between Sex Hormone-Binding Globulin and Bone Mineral Density: Insights From a Large-Scale Genomewide Cross-Trait Analysis. J Bone Miner Res. Published 13 September 2023. doi:10.
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