Yunfeng Yu, Xinyu Yang, Juan Deng, Jingyi Wu, Siyang Bai, Rong Yu
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引用次数: 0
Abstract
Objective: The role of immune cells in type 1 diabetes (T1D) is unclear. The aim of this study was to assess the causal effect of different immune cells on T1D using Mendelian randomization (MR).
Methods: A dataset of immune cell phenotypes (numbered from GCST0001391 to GCST0002121) was obtained from the European Bioinformatics Institute, while a T1D dataset (numbered finngen_R10_T1D) was obtained from FinnGen. Single nucleotide polymorphisms meeting the conditions were screened stepwise according to the assumptions of association, independence, and exclusivity. Inverse variance weighted was used as the main method for the MR analysis. MR-Egger was used to assess the horizontal pleiotropy of the results. Cochran's Q and the leave-one-out method were respectively used for the heterogeneity analysis and the sensitivity analysis of the results.
Results: MR analysis showed that effector memory (EM) double-negative (DN) (CD4-CD8-) %T cells [odds ratio (OR) = 1.157, 95% confidence interval (95% CI) = 1.016-1.318, p = 0.028, false discovery rate (FDR) = 0.899], EM CD8br %T cells (OR = 1.049, 95% CI = 1.003-1.098, p = 0.037, FDR = 0.902), CD28 on CD28+CD45RA+CD8br (OR = 1.334, 95% CI = 1.132-1.571, p = 0.001, FDR = 0.044), IgD+CD38dim %lymphocytes (OR = 1.045, 95% CI = 1.002-1.089, p = 0.039, FDR = 0.902), CD80 on monocytes (OR = 1.084, 95% CI = 1.013-1.161, p = 0.020, FDR = 0.834), SSC-A on plasmacytoid dendritic cells (pDCs) (OR = 1.174, 95% CI = 1.004-1.372, p = 0.044, FDR = 0.902), and FSC-A on pDCs (OR = 1.182, 95% CI = 1.011-1.382, p = 0.036, FDR = 0.902) were associated with an increased genetic susceptibility to T1D. Cochran's Q showed that there was heterogeneity for CD28 on the CD28+CD45RA+CD8br results (p = 0.043), whereas there was no heterogeneity for the other results (p ≥ 0.05). The sensitivity analysis showed that the MR analysis results were robust.
Conclusion: The MR analysis demonstrated that seven immune cell phenotypes were associated with an increased genetic susceptibility to T1D. These findings provide a new direction for the pathogenesis of and the drug development for T1D.
期刊介绍:
Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series.
In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology.
Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.