# Genetically determined body mass index is associated with diffuse large B‐cell lymphoma in polygenic and Mendelian randomization analyses

## TL;DR

This study finds a genetic link between higher body mass index and increased risk of diffuse large B-cell lymphoma, a type of non-Hodgkin lymphoma.

## Contribution

The study identifies a genetic association between BMI and diffuse large B-cell lymphoma using polygenic and Mendelian randomization analyses.

## Key findings

- Higher genetically determined BMI is linked to increased risk of diffuse large B-cell lymphoma.
- Mendelian randomization analysis supports the genetic link between BMI and diffuse large B-cell lymphoma.
- No significant associations were found with other non-Hodgkin lymphoma subtypes.

## Abstract

Obesity has been associated with non‐Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome‐wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist‐to‐hip ratio (WHR), and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05–1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (ORper SD = 1.12, 95% CI: 1.02–1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.

What's new?

Obesity has been linked to the risk of non‐Hodgkin lymphoma (NHL), but the evidence remains inconclusive. Here, the authors investigate the possibility of shared genetic risk factors between obesity and four common NHL types. Drawing on data from 8 genome‐wide association studies, they found that a higher genetically determined BMI was associated with a higher risk of just one NHL type, diffuse large B cell lymphoma (DLBCL). This positive association was confirmed using Mendelian randomization.