A Two-sample Mendelian Randomization Analysis Of Causal Association Between Body Mass Index And Lymphoma

Background: Previous observational studies have suggested that Body Mass Index(BMI)is associated with an increased risk of lymphoma,but the causal relationship between BMI and lymphoma remains uncertain given the confounding factors in clinical studies.We used two-sample Mendelian Radomization(MR)to analyze the association between BMI and lymphoma risk.Mendelian randomization can avoid the interference of confounding factors and reverse causal association in traditional observational studies,and provide a new way to explore the etiology of clinical diseases.Purpose: Based on the Genome Wide Association Study(GWAS)publicly published database,we used two-sample MR Analysis to investigate the causal relationship between BMI and risk of pan-lymphoma and Hodgkin’s lymphoma(HL),diffuse large B-cell lymphoma(DLBCL),follicular lymphoma(FL),and T/NK cell lymphoma respectively.Method: In the GWAS database published by GIANT Consortium,69 genetic variants were selected as Instrumental Variables(IV)of BMI after strict screening.For pan-lymphoma GWAS,the aggregated data from Biobank in UK were selected.GWAS for Hodgkin’s lymphoma,diffuse large B-cell lymphoma,follicular lymphoma,and T/NK cell lymphoma were all obtained from the Finn Gen consortium.We used a two-sample MR Analysis to estimate the causal effect of BMI and various types of lymphoma,Inverse Variance Weighted(IVW)of the random-effect model was selected as the main analysis method,and Weighted Median Estimator(WME)and MR-Egger method were used to enhance the research results.The heterogeneity test and pleiotropy test were further conducted to evaluate the reliability of the results.Results: There was no causal relationship between BMI and various lymphomas [BMI and pan-lymphoma: Odds Ratio(OR)=1.001,95% Confidence Interval(CI)=0.99-1.003,P =0.09;BMI and HL:OR=0.914,95%CI=0.429-1.946,P=0.82;BMI and DLBCL: OR=0.483,95%CI=0.177-1.314,P=0.15;BMI and FL:OR=1.064,95%CI=0.564-2.006,P=0.85;BMI and T/NK lymphoma: OR=0.945,95%CI=0.292-3.063,P=0.92],no heterogeneity or level pleiotropy was observed in the above results(p > 0.05).Conclusions: Based on the genetic perspective,no causal association between BMI and lymphoma was found in this study,and a larger sample size may be needed to further verify the association between the two.