Causal relationship between body mass index, type 2 diabetes and bone mineral density: Mendelian randomization

PLoS One. 2023 Oct 2;18(10):e0290530. doi: 10.1371/journal.pone.0290530. eCollection 2023.

Abstract

Objective: To reveal the relationship between Body Mass Index(BMI), type 2 diabetes, and bone mineral density(BMD) using a mendelian randomization (MR) approach.

Methods: GWAS data on BMI, type 2 diabetes, and BMD were selected from the IEU GWAS database at the University of Bristol.Univariable, multivariable, and mediated MR analyses were used to explore the relationship between BMI, type 2 diabetes, and BMD. beta(β) values were given, and three methods, including inverse variance weighting, MR-Egger regression, and weighted median, were used in this analysis.

Results: Univariable mendelian randomization (UVMR) results showed that BMI and type 2 diabetes were positively associated with BMD. However, the association between BMI and BMD was insignificant in the multivariable Mendelian randomization (MVMR) analysis, while that between type 2 diabetes and BMD remained significant. Mediated MR analysis indicated that type 2 diabetes mediated the regulation of BMD by BMI.

Conclusion: This study provides evidence supporting a positive causal association between BMI, type 2 diabetes, and BMD. Type 2 diabetes acts as a mediator in the regulation of BMD by BMI, indicating that both BMI and type 2 diabetes exert a protective influence on BMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Mass Index
  • Bone Density* / genetics
  • Causality
  • Diabetes Mellitus, Type 2* / genetics
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Polymorphism, Single Nucleotide

Grants and funding

1.2022 Hubei Provincial Education Department scientific research program guidance projects 2. 2021 Hubei Provincial Education Department scientific research program funding projects in young talent projects.