Abstract
Observational studies suggest a link between depression and osteoporosis, but these may be subject to confounding and reverse causality. In this two-sample Mendelian randomization analysis, we included the large meta-analysis of genome-wide association studies for depression among 807,553 individuals (246,363 cases and 561,190 controls) of European descent, the large meta-analysis to identify genetic variants associated with femoral neck bone mineral density (FN-BMD), forearm BMD (FA-BMD) and lumbar spine BMD (LS-BMD) among 53,236 individuals of European ancestry, and the GWAS summary data of heel BMD (HE-BMD) and fracture among 426,824 individuals of European ancestry. The results revealed that genetic predisposition towards depression showed no causal effect on FA-BMD (beta-estimate: 0.091, 95% confidence interval [CI] − 0.088 to 0.269, SE:0.091, P value = 0.320), FN-BMD (beta-estimate: 0.066, 95% CI − 0.016 to 0.148, SE:0.042, P value = 0.113), LS-BMD (beta-estimate: 0.074, 95% CI − 0.029 to 0.177, SE:0.052, P value = 0.159), HE-BMD (beta-estimate: 0.009, 95% CI − 0.043 to 0.061, SE:0.027, P value = 0.727), or fracture (beta-estimate: 0.008, 95% CI − 0.071 to 0.087, SE:0.041, P value = 0.844). These results were also confirmed by multiple sensitivity analyses. Contrary to the findings of observational studies, our results do not reveal a causal role of depression in osteoporosis or fracture.
Highlights
The United Nations have predicted that the ratio of people aged more than 65 years to those aged 15–64 years will triple globally by 2100 [1]
Among the diseases associated with musculoskeletal conditions, osteoporosis is a common, aging-related disease characterized by decreased bone mineral density (BMD) and increased risk of fracture [3,4,5,6]
single nucleotide polymorphisms (SNPs) for forearm BMD (FA-BMD), SNPs for femoral neck bone mineral density (FN-BMD) and lumbar spine BMD (LS-BMD), 74 SNPs for heel BMD (HE-BMD) and fracture were used as the instrumental variables (Table 1)
Summary
The United Nations have predicted that the ratio of people aged more than 65 years to those aged 15–64 years will triple globally by 2100 [1]. Several meta-analyses included cross-sectional or case–control studies to investigate the association of depression and osteoporosis, and found that depression might be a significant risk factor for low BMD and fracture, but the results were not consistent [15,16,17,18]. None of these studies assessed the their association in the prospective cohort design, and these studies were limited by confounding factors and reverse causality
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