biostudies-literatureWang YMajor Central Government Projects with Significant Budgetary Impact, Sustainable Utilization Capacity Building Project for Precious Chinese Medicinal ResourcesMayinglong Pharmaceutical Group Co., Ltd.267-279https://www.ebi.ac.uk/biostudies/studies/S-EPMC12863003biostudies-literatureUnknown17(2)<h4>Aims/introduction</h4>Leukocytes are implicated in the inflammatory cascades of diabetic retinopathy (DR), but their causal roles remain ambiguous. This study employed a two-sample Mendelian randomization (MR) analysis to dissect the causal effects of circulating leukocyte counts on DR risk.<h4>Materials and methods</h4>We utilized summary statistics from large-scale genome-wide association studies (GWAS) for five leukocyte subtypes and DR in European-ancestry populations. The inverse-variance weighted (IVW) method was primary, supported by comprehensive sensitivity analyses including MR-Egger, weighted median, and the MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) test to ensure result robustness.<h4>Results</h4>A total of 2,136 leukocyte-related SNPs were extracted as instrumental variables for causal inference. MR analysis revealed that increased lymphocyte counts are associated with reduced DR risk (IVW OR = 0.93, 95% CI = 0.86-0.99, P = 0.03), while the initial association between higher eosinophil counts and DR risk (IVW OR = 1.11, 95% CI = 1.03-1.19, P < 0.01) was attenuated following correction for outliers. No significant associations were observed for basophil, monocyte, or neutrophil counts. Sensitivity analyses found no evidence of pleiotropy or substantial influence from single SNPs.<h4>Conclusions</h4>Our findings provide genetic evidence supporting a potential causal association between lymphocyte counts and diabetic retinopathy risk, while the association for eosinophil counts was attenuated after correction for outliers. These results highlight the importance of further investigating the physiological role of lymphocytes in diabetic retinopathy to inform effective prevention and treatment strategies.Journal of diabetes investigationCausal association between circulating leukocyte characteristics and diabetic retinopathy based on two-sample Mendelian randomization.PMC12863003303-02-3172060302-2303-21Wu JGuo LWu LZhang XGao YWang YWang ZShang SfalseCausal association between circulating leukocyte characteristics and diabetic retinopathy based on two-sample Mendelian randomization.<h4>Aims/introduction</h4>Leukocytes are implicated in the inflammatory cascades of diabetic retinopathy (DR), but their causal roles remain ambiguous. This study employed a two-sample Mendelian randomization (MR) analysis to dissect the causal effects of circulating leukocyte counts on DR risk.<h4>Materials and methods</h4>We utilized summary statistics from large-scale genome-wide association studies (GWAS) for five leukocyte subtypes and DR in European-ancestry populations. The inverse-variance weighted (IVW) method was primary, supported by comprehensive sensitivity analyses including MR-Egger, weighted median, and the MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) test to ensure result robustness.<h4>Results</h4>A total of 2,136 leukocyte-related SNPs were extracted as instrumental variables for causal inference. MR analysis revealed that increased lymphocyte counts are associated with reduced DR risk (IVW OR = 0.93, 95% CI = 0.86-0.99, P = 0.03), while the initial association between higher eosinophil counts and DR risk (IVW OR = 1.11, 95% CI = 1.03-1.19, P < 0.01) was attenuated following correction for outliers. No significant associations were observed for basophil, monocyte, or neutrophil counts. Sensitivity analyses found no evidence of pleiotropy or substantial influence from single SNPs.<h4>Conclusions</h4>Our findings provide genetic evidence supporting a potential causal association between lymphocyte counts and diabetic retinopathy risk, while the association for eosinophil counts was attenuated after correction for outliers. These results highlight the importance of further investigating the physiological role of lymphocytes in diabetic retinopathy to inform effective prevention and treatment strategies.2026-01-01T00:00:00Z2026 Feb2026-06-24T03:06:05.861Z2026-06-24T03:04:11.306ZS-EPMC128630034131102810.1111/jdi.70196