Academic Journal
Causal relationship between genetically predicted white blood cell count and systemic lupus erythematosus: A Mendelian randomization study.
| Τίτλος: | Causal relationship between genetically predicted white blood cell count and systemic lupus erythematosus: A Mendelian randomization study. |
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| Συγγραφείς: | Wang XF; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China., Zhang L; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China., Yao QY; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China., Liu J; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China., Dang ZX; School of Cyberspace Security, Xi'an University of Posts and Telecommunications, Xi'an, Shaanxi, China., Zhu YH; Institute of Endemic Diseases, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China. |
| Πηγή: | Medicine [Medicine (Baltimore)] 2026 Sep 25; Vol. 105 (39), pp. e50878. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 2985248R Publication Model: Print Cited Medium: Internet ISSN: 1536-5964 (Electronic) Linking ISSN: 00257974 NLM ISO Abbreviation: Medicine (Baltimore) Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Hagerstown, Md : Lippincott Williams & Wilkins |
| Ιατρικοί όροι (MeSH): | Lupus Erythematosus, Systemic*/genetics , Lupus Erythematosus, Systemic*/blood , Mendelian Randomization Analysis*, Humans ; Leukocyte Count ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease |
| Περίληψη: | Observational studies have suggested an association between white blood cell (WBC) count and systemic lupus erythematosus (SLE). However, the causal relationship remains uncertain because of potential confounding factors. This Mendelian randomization (MR) study aimed to investigate the causal effect of WBC count on SLE risk by using genetic instruments. Genetically predicted higher WBC counts were associated with a reduced risk of SLE (inverse-variance weighted [IVW]: odds ratio = 0.384, 95% confidence interval = 0.160-0.920, P = .031; weighted median: odds ratio = 0.326, 95% confidence interval = 0.124-0.859, P = .023). MR-Egger regression revealed no evidence of horizontal pleiotropy (intercept, P = .705), and MR polygenic residual sum and outlier (MR-PRESSO) detected 4 outliers. After outlier removal, heterogeneity decreased, and the IVW and weighted median estimates remained significant (beta = -0.96, P = .03; beta = -1.12, P = .023, respectively). We conducted a 2-sample MR analysis using summary statistics from genome-wide association studies (GWAS) of European ancestry: WBC count (GWAS ID: ieu-b-30, N = 563,946) and SLE (GWAS ID: ieu-a-815, 14,267 cases, and 43,047 controls). Sixty-five independent single-nucleotide polymorphisms (P < 5 × 10-8, clumped at r2 < 0.001) were selected as instrumental variables, with a mean F statistic of 28.6, indicating strong instrument strength. Analyses were performed using R statistical software (R Foundation for Statistical Computing) with the TwoSampleMR and MR-PRESSO packages. The primary analytical methods included IVW, weighted median, and MR-Egger regression. Sensitivity analyses included Cochran Q test for heterogeneity, MR-PRESSO outlier correction, and leave-one-out validation to ensure robustness. This MR analysis supports an independent causal protective effect of genetically predicted higher WBC counts on SLE risk. These findings should not be extrapolated as evidence for therapeutic leukocyte elevation, nor do they alter the clinical management of leukopenia observed in active SLE or during immunosuppressive therapy. The genetic signal likely reflects broader immune homeostatic regulation rather than lineage-specific effects, the mechanistic basis of which warrants dedicated functional investigation. (Copyright © 2026 the Author(s). Published by Wolters Kluwer Health, LLC.) |
| Competing Interests: | The authors have no conflicts of interest to declare. |
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| Grant Information: | 81441016 he National Natural Science Foundation of China; 2020SF-262 Key R&D Plan in Shaanxi Province of China; 2019SF-200 Key R&D Plan in Shaanxi Province of China |
| Contributed Indexing: | Keywords: GWAS; Mendelian randomization; R software; causal inference; systemic lupus erythematosus; white blood cell count |
| Entry Date(s): | Date Created: 20260926 Date Completed: 20260926 Latest Revision: 20260930 |
| Update Code: | 20260930 |
| PubMed Central ID: | PMC13619244 |
| DOI: | 10.1097/MD.0000000000050878 |
| PMID: | 42798072 |
| Βάση Δεδομένων: | MEDLINE |
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