AUTHOR=Ye Yunyan , Dai Lei , Gu Hong , Yang Lan , Xu Zhangxing , Li Zhiguo 

TITLE=The causal relationship between immune cells and diabetic retinopathy: a Mendelian randomization study

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1381002

DOI=10.3389/fimmu.2024.1381002

ISSN=1664-3224

ABSTRACT=Purpose: To explore the causal relationship between immune cells and diabetic retinopathy (DR) using single nucleotide polymorphisms (SNPs) as an instrumental variable and Mendelian randomization (MR).
Methods: Statistical data were collected from a publicly available genome-wide association study (GWAS), and SNPs that were significantly associated with immune cells were used as instrumental variables (IVs). Inverse variance weighted (IVW) and MR‒Egger regression were used for MR analysis. Sensitivity analysis was used to test the heterogeneity, horizontal pleiotropy, and stability of the results.
Results: We investigated the causal relationship between 731 immune cells and DR risk. All the GWAS data were obtained from European populations and from males and females. The IVW analysis revealed that HLA DR on CD14+ CD16- monocytes, HLA DR on CD14+ monocytes, HLA DR on CD33-HLA DR+, HLA DR on CD33+ HLA DR+ CD14- on CD33+ HLA DR+ CD14dim and HLA DR on myeloid dendritic cells may increase the risk of DR (P<0.05). The HLA DR to CD14-CD16- cells, the monocytic myeloid-derived suppressor cell absolute count, the SSC-A count of CD4+ T cells, and the terminally differentiated CD4+ T cells may be protective factors against DR (P<0.05). Sensitivity analysis indicated no heterogeneity or pleiotropy among the selected SNPs. Furthermore, gene annotation of the SNPs revealed significant associations with 10 genes related to the risk of developing PDR and potential connections with 12 other genes related to PDR.
Conclusion: Monocytes and T cells may serve as new biomarkers or therapeutic targets, leading to the development of new treatment options for managing DR.