The causal effect of adipose tissue on Hodgkin's lymphoma: two-sample Mendelian randomization study and validation.

ABSTRACT

Background: Extensive research has been conducted on the correlation between adipose tissue and the risk of malignant lymphoma. Despite numerous observational studies exploring this connection, uncertainty remains regarding a causal relationship between adipose tissue and malignant lymphoma. Methods: The increase or decrease in adipose tissue was represented by the height of BMI. The BMI and malignant lymphoma genome-wide association studies (GWAS) used a summary dataset from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) that met the criteria of P <5e-8 and LD of r2 = 0.001 in the BMI GWAS were chosen as genetic instrumental variants (IVs). Proxy SNPs with LD of r2 > 0.8 were identified, while palindromic and outlier SNPs were excluded. Mendelian randomization (MR) analysis used five methods, including inverse-variance weighted (IVW) model, weighted median (WM), MR-Egger, simple mode, and weighted mode. Sensitivity assessments included Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis. Participants randomly selected by the National Center for Health Statistics (NHANSE) and newly diagnosed HL patients at Fujian Medical University Union Hospital were used for external validation. Results: The results of the MR analysis strongly supported the causal link between BMI and Hodgkin's lymphoma (HL). The research demonstrated that individuals with lower BMI face a significantly increased risk of developing HL, with a 91.65% higher risk (ORIVW = 0.0835, 95% CI 0.0147 - 0.4733, P = 0.005). No signs of horizontal or directional pleiotropy were observed in the MR studies. The validation results aligned with the results from the MR analysis (OR = 0.871, 95% CI 0.826 - 0.918, P< 0.001). And there was no causal relationship between BMI and non-Hodgkin's lymphoma (NHL). Conclusions: The MR analysis study demonstrated a direct correlation between lower BMI and HL. This suggested that a decrease in adipose tissue increases the risk of developing HL. Nevertheless, further research is essential to grasp the underlying mechanism of this causal association comprehensively.