White blood cells and type 2 diabetes: A Mendelian randomization study.
<h4>Background</h4>Observational studies have demonstrated an association between white blood cells (WBC) subtypes and type 2 diabetes (T2D) risk. However, it is unknown whether this relationship is causal. We used Mendelian randomization (MR) to investigate the causal effect of WBC subt...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0296701 |
| _version_ | 1797266327316987904 |
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| author | Yaru Bi Yuan Gao Yao Xie Meng Zhou Zhiyuan Liu Suyan Tian Chenglin Sun |
| author_facet | Yaru Bi Yuan Gao Yao Xie Meng Zhou Zhiyuan Liu Suyan Tian Chenglin Sun |
| author_sort | Yaru Bi |
| collection | DOAJ |
| description | <h4>Background</h4>Observational studies have demonstrated an association between white blood cells (WBC) subtypes and type 2 diabetes (T2D) risk. However, it is unknown whether this relationship is causal. We used Mendelian randomization (MR) to investigate the causal effect of WBC subtypes on T2D and glycemic traits.<h4>Methods</h4>The summary data for neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts were extracted from a recent genome-wide association study (n = 173,480). The DIAGRAM and MAGIC consortia offered summary data pertaining to T2D and glycemic characteristics, including fasting glucose (FG) (n = 133,010), glycosylated hemoglobin (HbA1c) (n = 46,368), and homeostatic model assessment-estimated insulin resistance (HOMA-IR) (n = 37,037). A series of MR analyses (univariable MR, multivariable MR, and reverse MR) were used to investigate the causal association of different WBC subtypes with T2D and glycemic traits.<h4>Results</h4>Using the inverse-variance weighted method, we found one standard deviation increases in genetically determined neutrophil [odd ratio (OR): 1.086, 95% confidence interval (CI): 0.877-1.345], lymphocyte [0.878 (0.766-1.006)], monocyte [1.010 (0.906-1.127)], eosinophil [0.995 (0.867-1.142)], and basophil [0.960 (0.763-1.207)] were not causally associated with T2D risk. These findings were consistent with the results of three pleiotropy robust methods (MR-Egger, weighted median, and mode-based estimator) and multivariable MR analyses. Reverse MR analysis provided no evidence for the reverse causation of T2D on WBC subtypes. The null causal effects of WBC subtypes on FG, HbA1c, and HOMA-IR were also identified.<h4>Conclusions</h4>WBCs play no causal role in the development of insulin resistance and T2D. The observed association between these factors may be explained by residual confounding. |
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| format | Article |
| id | doaj.art-05b8cd577e96429ba28a79be6f6ae353 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-25T00:58:56Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-05b8cd577e96429ba28a79be6f6ae3532024-03-11T05:32:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01193e029670110.1371/journal.pone.0296701White blood cells and type 2 diabetes: A Mendelian randomization study.Yaru BiYuan GaoYao XieMeng ZhouZhiyuan LiuSuyan TianChenglin Sun<h4>Background</h4>Observational studies have demonstrated an association between white blood cells (WBC) subtypes and type 2 diabetes (T2D) risk. However, it is unknown whether this relationship is causal. We used Mendelian randomization (MR) to investigate the causal effect of WBC subtypes on T2D and glycemic traits.<h4>Methods</h4>The summary data for neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts were extracted from a recent genome-wide association study (n = 173,480). The DIAGRAM and MAGIC consortia offered summary data pertaining to T2D and glycemic characteristics, including fasting glucose (FG) (n = 133,010), glycosylated hemoglobin (HbA1c) (n = 46,368), and homeostatic model assessment-estimated insulin resistance (HOMA-IR) (n = 37,037). A series of MR analyses (univariable MR, multivariable MR, and reverse MR) were used to investigate the causal association of different WBC subtypes with T2D and glycemic traits.<h4>Results</h4>Using the inverse-variance weighted method, we found one standard deviation increases in genetically determined neutrophil [odd ratio (OR): 1.086, 95% confidence interval (CI): 0.877-1.345], lymphocyte [0.878 (0.766-1.006)], monocyte [1.010 (0.906-1.127)], eosinophil [0.995 (0.867-1.142)], and basophil [0.960 (0.763-1.207)] were not causally associated with T2D risk. These findings were consistent with the results of three pleiotropy robust methods (MR-Egger, weighted median, and mode-based estimator) and multivariable MR analyses. Reverse MR analysis provided no evidence for the reverse causation of T2D on WBC subtypes. The null causal effects of WBC subtypes on FG, HbA1c, and HOMA-IR were also identified.<h4>Conclusions</h4>WBCs play no causal role in the development of insulin resistance and T2D. The observed association between these factors may be explained by residual confounding.https://doi.org/10.1371/journal.pone.0296701 |
| spellingShingle | Yaru Bi Yuan Gao Yao Xie Meng Zhou Zhiyuan Liu Suyan Tian Chenglin Sun White blood cells and type 2 diabetes: A Mendelian randomization study. PLoS ONE |
| title | White blood cells and type 2 diabetes: A Mendelian randomization study. |
| title_full | White blood cells and type 2 diabetes: A Mendelian randomization study. |
| title_fullStr | White blood cells and type 2 diabetes: A Mendelian randomization study. |
| title_full_unstemmed | White blood cells and type 2 diabetes: A Mendelian randomization study. |
| title_short | White blood cells and type 2 diabetes: A Mendelian randomization study. |
| title_sort | white blood cells and type 2 diabetes a mendelian randomization study |
| url | https://doi.org/10.1371/journal.pone.0296701 |
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