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

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.

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Item Type:	Article
Authors/Creators:	Moore, Amy Kane, Eleanor https://orcid.org/0000-0002-7438-9982 Teras, Lauren R. Machiela, Mitchell J. Arias, Joshua Panagiotou, Orestis A. Monnereau, Alain Doo, Nicole Wong Wang, Zhaoming Slager, Susan L. Vermeulen, Roel C.H. Vajdic, Claire M. Smedby, Karin E. Spinelli, John J. Vijai, Joseph Giles, Graham G. Link, Brian K. Arslan, Alan A. Nieters, Alexandra Bracci, Paige M. Camp, Nicola J. Salles, Gilles Cozen, Wendy Hjalgrim, Henrik De Vivo, Immaculata Adami, Hans Olov Albanes, Demetrius Becker, Nikolaus Benavente, Yolanda Bisanzi, Simonetta Boffetta, Paolo Brennan, Paul Brooks-Wilson, Angela R. Canzian, Federico Clavel, Jacqueline Conde, Lucia Cox, David G. Curtin, Karen Foretova, Lenka Ghesquières, Hervé Glimelius, Bengt Habermann, Thomas M. Hofmann, Jonathan N. Lan, Qing Liebow, Mark Lincoln, Anne Maynadie, Marc McKay, James Melbye, Mads Miligi, Lucia Milne, Roger L. Molina, Thierry J. Morton, Lindsay M. North, Kari E. Offit, Kenneth Padoan, Marina Piro, Sara Patel, Alpa V. Purdue, Mark P. Ravichandran, Vignesh Riboli, Elio Severson, Richard K. Southey, Melissa C. Staines, Anthony Tinker, Lesley F. Travis, Ruth C. Wang, Sophia S. Weiderpass, Elisabete Weinstein, Stephanie Zheng, Tongzhang Chanock, Stephen J. Rothman, Nathaniel Birmann, Brenda M. Cerhan, James R. Berndt, Sonja I.
Copyright, Publisher and Additional Information:	Publisher Copyright: © 2025 International Agency for Research on Cancer; licensed by UICC and The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Dates:	Accepted: 7 May 2024 Published (online): 5 September 2025 Published: 1 January 2026
Institution:	The University of York
Academic Units:	The University of York > Faculty of Sciences (York) > Health Sciences (York) The University of York > Faculty of Sciences (York) > Psychology (York) The University of York > Faculty of Sciences (York) > Electronic Engineering (York)
Date Deposited:	11 Feb 2026 13:00
Last Modified:	11 Feb 2026 13:01
Published Version:	https://doi.org/10.1002/ijc.70039
Status:	Published
Refereed:	Yes
Identification Number:	10.1002/ijc.70039
Related URLs:	http://www.scopus.com/inward/record.url?...
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:237849

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

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