| Title: | Bone mineral density and risk of type 2 diabetes and coronary heart disease: A Mendelian randomization study |
| Journal: | Wellcome Open Res |
| Published: | 22 Aug 2017 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/28989980/ |
| DOI: | https://doi.org/10.12688/wellcomeopenres.12288.1 |
Publication 1505
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Abstract
Observational studies have demonstrated positive associations between bone mineral density and risk of type 2 diabetes (T2D), but its relationship with risk of coronary heart disease (CHD) is unclear. Moreover, the causal relevance of BMD for both T2D and CHD cannot be fully addressed by traditional observational studies which are typically constrained by residual confounding and reverse causality bias. In current study, we conducted a genome-wide association study of estimated heel bone mineral density (eBMD), assessed by quantitative ultrasound, in the interim release of ~150k UK Biobank participants and examined the relationships of eBMD-associated SNPs with T2D and CHD through Mendelian randomization analyses. We identify 235 independent genetic markers or single nucleotide polymorphisms associated at p<5 10-8 with eBMD in ~116k individuals from the UKB. Using the 235 SNPs as genetic instrumental variables, we demonstrate a causal relationship between higher eBMD and lower risk of fracture (Odds Ratio 0.65; 95% CI: 0.62 to 0.68). We provide the evidences showing that higher genetically instrumented eBMD was associated with higher risks of both T2D (OR 1.08; 95%CI 1.02 to 1.14) and CHD (OR 1.05; 95%CI 1.00 to 1.10). Increased eBMD were also causally associated with lower plasma levels of HDL-cholesterol and increased insulin resistance. The findings of the present study suggest that higher bone density, measured by eBMD, may have an adverse effect on risk of cardiometabolic diseases, which may well have implications for patient care. In conclusion, Mendelian randomization provides evidence of a modest casual effect of elevated bone mineral density (assessed by quantitative ultrasound of heel) on risk of both T2D and CHD, which may be partially mediated by insulin resistance. The findings of this study add to the growing evidence-base suggesting a possible role of bone endocrine function in the pathogenesis of both type 2 diabetes and coronary heart disease.1 Author
- Gan W et al.
1 Application
| Application ID | Title |
|---|---|
| 9161 | Type 2 diabetes: using genetic discovery to drive biological inference and translational opportunities. |
Enabling scientific discoveries that improve human health