Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses
Publication date
2026-01-01
Authors
Moore, Amy
Kane, Eleanor
Teras, Lauren R
Machiela, Mitchell J
Arias, Joshua
Panagiotou, Orestis A
Monnereau, Alain
Doo, Nicole Wong
Wang, Zhaoming
Slager, Susan L
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Supervisors
Document Type
Article
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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 (OR per 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.
Keywords
Adiposity/genetics, Body Mass Index, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Leukemia, Lymphocytic, Chronic, B-Cell/genetics, Lymphoma, Follicular/genetics, Lymphoma, Large B-Cell, Diffuse/genetics, Male, Mendelian Randomization Analysis, Middle Aged, Multifactorial Inheritance, Obesity/genetics, Polymorphism, Single Nucleotide, Risk Factors, Waist-Hip Ratio, SDG 3 - Good Health and Well-being
Citation
Moore, A, Kane, E, Teras, L R, Machiela, M J, Arias, J, Panagiotou, O A, Monnereau, A, Doo, N W, Wang, Z, Slager, S L, Vermeulen, R C H, Vajdic, C M, Smedby, K E, Spinelli, J J, Vijai, J, Giles, G G, Link, B K, Arslan, A A, Nieters, A, Bracci, P M, Camp, N J, Salles, G, Cozen, W, Hjalgrim, H, De Vivo, I, Adami, H-O, Albanes, D, Becker, N, Benavente, Y, Bisanzi, S, Boffetta, P, Brennan, P, Brooks-Wilson, A R, Canzian, F, Clavel, J, Conde, L, Cox, D G, Curtin, K, Foretova, L, Ghesquières, H, Glimelius, B, Habermann, T M, Hofmann, J N, Lan, Q, Liebow, M, Lincoln, A, Maynadie, M, McKay, J, Melbye, M, Miligi, L, Milne, R L, Molina, T J, Morton, L M, North, K E, Offit, K, Padoan, M, Piro, S, Patel, A V, Purdue, M P, Ravichandran, V, Riboli, E, Severson, R K, Southey, M C, Staines, A, Tinker, L F, Travis, R C, Wang, S S, Weiderpass, E, Weinstein, S, Zheng, T, Chanock, S J, Rothman, N, Birmann, B M, Cerhan, J R & Berndt, S I 2026, 'Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses', International Journal of Cancer, vol. 158, no. 1, pp. 45-59. https://doi.org/10.1002/ijc.70039