Causal relationship between type 2 diabetes mellitus and bone mineral density: a Mendelian randomization study in an East Asian population

Abstract

Summary It remains unclear whether the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) reflects causality in East Asian populations. Herein, a Mendelian randomization study conducted in East Asian population enhances the current clinical cognition that T2DM is not associated with reduction in BMD. Purpose A Mendelian randomization (MR) approach was utilized to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in East Asian populations. Methods Genome-wide association study summary data from BioBank Japan were used to identify genetic variants strongly related to T2DM risk (36,614 cases and 155,150 controls) and osteoporosis (7788 cases and 204,665 controls). Heel BMD GWAS data of 1260 East Asian people from ieu open gwas project was considered as a second outcome. Inverse variance-weighted (IVW) analysis was mainly applied; MR-Egger and the weighted median were also used to obtain robust estimates. A series of sensitivity analyses including Cochran’s Q test, MR-Egger regression, and leave-one-out analysis were used to detect pleiotropy or heterogeneity. Results In the main analysis, IVW estimates indicated that T2DM significantly associated with the risk of osteoporosis (odds ratio = 0.92, 95% CI: 0.86–0.99, p = 0.016) and with higher BMD (OR: 1.25, 95% CI: 1.06–1.46, p = 6.49 × 10 −3 ). Results of comprehensive sensitivity analysis were consistent with the main causality estimate. Horizontal pleiotropy and heterogeneity were absent in our MR study. Conclusions T2DM is not associated with reduction in BMD in terms of genetic polymorphism in East Asian populations. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-023-06807-6.

Causal relationship between type 2 diabetes and BMD: a Mendelian randomization study

“…Previous studies have conducted Mendelian randomization (MR) studies in East Asian populations, which con rmed a causal relationship between type 2 diabetes and higher BMD, but no causal relationship with decreased BMD. However, these studies did not differentiate between different sites of BMD [5]. In contrast to the conclusion of another MR study, which suggested that type 2 diabetes is causally associated with femoral neck BMD but not with lumbar spine BMD, our results are inconsistent with this nding [6].…”

Causal association between major depressive disorder and venous thromboembolism: a bidirectional mendelian randomization study

“…Finally, a multivariable MR analysis was performed to assess the causal relationship between MDD and VTE, adjusting for education and BMI in our models to assess the effect of potential confounders. The multivariable MR simultaneously considers multiple exposure factors; it limits the corresponding effects of SNP exposure on the characteristics of other assumed risk factors and eliminates possible biases ( Huang G. et al, 2023 ).…”

Causal relationship between serum uric acid and cardiovascular disease: a Mendelian randomization study

“…As genetic variants are assigned randomly at conception, MR circumvents confounding factors and reverse causality, common issues in traditional observational studies (13). Additionally, the precision of gene variant sequencing signi cantly reduces bias from measurement errors (14). This study employed two-sample MR analysis, utilizing the pooled statistics from genome-wide association studies (GWAS), to investigate the causal relationship between serum uric acid and cardiovascular disease (CVD), thereby contributing novel insights for CVD prevention.…”