Causal relationships between body composition and hematological malignancies: a multivariable mendelian randomization analysis.

Background: The relationship between body composition and hematological malignancies is poorly understood. Using mendelian randomization (MR) analysis, this study aimed to assess the genetic associations between body composition and hematological malignancies.

Methods: Data from the UK Biobank Genome-Wide Association Studies database, which includes approximately 500,000 participants aged 40-69 years, were utilized. Multivariable MR analysis and the inverse-variance weighted (IVW) method were employed to assess the causal link between exposures and outcomes. Sensitivity analyses were performed to evaluate the heterogeneity and pleiotropy of the instrumental variables.

Results: The univariable MR analysis revealed that specific body composition parameters, including arm fat-free mass (left and right), trunk-predicted mass, whole-body fat-free mass, and whole-body water mass, were associated with an increased leukemia risk. Arm fat-free mass (right) and fat mass (left and right); leg fat-free mass (left and right) and fat mass (left and right); trunk fat-free mass, fat mass, and predicted mass; and whole-body fat-free mass, fat mass, and water mass were associated with an increased lymphoma risk. However, no causal relationship was observed between body composition parameters and multiple myeloma. In the multivariable MR analysis, height [odds ratio (OR) = 1.004, p = 0.040] was identified as an independent risk factor for lymphoma, while the waist-to-hip ratio (OR = 1.003, p = 0.004) increased the risk of multiple myeloma.

Conclusion: Height increases the risk of lymphoma, while the waist-to-hip ratio is a risk factor for multiple myeloma. These findings offer further evidence supporting a causal relationship between body composition and hematological malignancies.