Causal association between endocrine diseases and lymphoid malignancies explored through two-sample Mendelian randomization analysis

Abstract Endocrine diseases are suspected contributors to lymphoid malignancies, but their precise association is unclear. This study aimed to investigate the causal relationship between various endocrine diseases—specifically type 2 diabetes, obesity, diabetic hypoglycemia, hyperlipidemia, and hype...

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Main Authors: Chenze Zhao, Yu Zhang, Lili Qian, Qing Guo, Ni Zhu
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-99010-y
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author Chenze Zhao
Yu Zhang
Lili Qian
Qing Guo
Ni Zhu
author_facet Chenze Zhao
Yu Zhang
Lili Qian
Qing Guo
Ni Zhu
author_sort Chenze Zhao
collection DOAJ
description Abstract Endocrine diseases are suspected contributors to lymphoid malignancies, but their precise association is unclear. This study aimed to investigate the causal relationship between various endocrine diseases—specifically type 2 diabetes, obesity, diabetic hypoglycemia, hyperlipidemia, and hyperthyroidism—and lymphoid malignancies, including lymphocytic leukemia and non-Hodgkin’s lymphoma with subtypes like diffuse large B-cell lymphoma and follicular lymphoma. Utilizing data from genome-wide association studies, a two-sample Mendelian randomization analysis was performed. The primary approach involved the inverse-variance weighted method, supplemented by other robust techniques such as the weighted median and MR-Egger regression to ensure reliability. The analysis indicated a significant causal connection between genetically predicted diabetic hypoglycemia and lymphocytic leukemia (Odds ratio = 1.0004, 95% Confidence interval = 1-1.0007, P = 0.03). Conversely, no associations were found for the other endocrine diseases with lymphoid malignancies (P > 0.05 for all). The findings suggest that while diabetic hypoglycemia may influence lymphocytic leukemia risk, further research is necessary to clarify the roles of other endocrine diseases in lymphoid malignancies, including cross-population validations and biological investigations.
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spelling doaj-art-98adcbff42fc406bb4e49bdcae9c6b712025-08-20T03:13:54ZengNature PortfolioScientific Reports2045-23222025-04-0115111210.1038/s41598-025-99010-yCausal association between endocrine diseases and lymphoid malignancies explored through two-sample Mendelian randomization analysisChenze Zhao0Yu Zhang1Lili Qian2Qing Guo3Ni Zhu4Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeDepartment of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)Department of Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)International Mongolia Hospital of Inner MongoliaDepartment of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)Abstract Endocrine diseases are suspected contributors to lymphoid malignancies, but their precise association is unclear. This study aimed to investigate the causal relationship between various endocrine diseases—specifically type 2 diabetes, obesity, diabetic hypoglycemia, hyperlipidemia, and hyperthyroidism—and lymphoid malignancies, including lymphocytic leukemia and non-Hodgkin’s lymphoma with subtypes like diffuse large B-cell lymphoma and follicular lymphoma. Utilizing data from genome-wide association studies, a two-sample Mendelian randomization analysis was performed. The primary approach involved the inverse-variance weighted method, supplemented by other robust techniques such as the weighted median and MR-Egger regression to ensure reliability. The analysis indicated a significant causal connection between genetically predicted diabetic hypoglycemia and lymphocytic leukemia (Odds ratio = 1.0004, 95% Confidence interval = 1-1.0007, P = 0.03). Conversely, no associations were found for the other endocrine diseases with lymphoid malignancies (P > 0.05 for all). The findings suggest that while diabetic hypoglycemia may influence lymphocytic leukemia risk, further research is necessary to clarify the roles of other endocrine diseases in lymphoid malignancies, including cross-population validations and biological investigations.https://doi.org/10.1038/s41598-025-99010-yEndocrine diseasesLymphoid malignanciesMendelian randomizationCausal relationshipGenetic associationSNPs
spellingShingle Chenze Zhao
Yu Zhang
Lili Qian
Qing Guo
Ni Zhu
Causal association between endocrine diseases and lymphoid malignancies explored through two-sample Mendelian randomization analysis
Scientific Reports
Endocrine diseases
Lymphoid malignancies
Mendelian randomization
Causal relationship
Genetic association
SNPs
title Causal association between endocrine diseases and lymphoid malignancies explored through two-sample Mendelian randomization analysis
title_full Causal association between endocrine diseases and lymphoid malignancies explored through two-sample Mendelian randomization analysis
title_fullStr Causal association between endocrine diseases and lymphoid malignancies explored through two-sample Mendelian randomization analysis
title_full_unstemmed Causal association between endocrine diseases and lymphoid malignancies explored through two-sample Mendelian randomization analysis
title_short Causal association between endocrine diseases and lymphoid malignancies explored through two-sample Mendelian randomization analysis
title_sort causal association between endocrine diseases and lymphoid malignancies explored through two sample mendelian randomization analysis
topic Endocrine diseases
Lymphoid malignancies
Mendelian randomization
Causal relationship
Genetic association
SNPs
url https://doi.org/10.1038/s41598-025-99010-y
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