Bidirectional Mendelian randomization analysis of the relationships between blood cell phenotypes, genetic variants,
1Emergency Department, Liuzhou Municipal Liutie Central Hospital, Liuzhou, Guangxi, China.
Abstract:
Based on a bidirectional two-sample Mendelian randomization (MR) analysis of 91 blood cell phenotypes and systemic lupus erythematosus (SLE), this study provides genetic evidence for a complex causal interplay between specific immune cell functions and SLE susceptibility. Forward MR analysis identified 4 perturbation responses - involving eosinophils (response to colchicine), neutrophils (response to potassium chloride and lipopolysaccharide), and platelets (response to nigericin) - as causally linked to SLE risk, with 3 increasing and 1 decreasing susceptibility. Reverse MR analysis revealed that genetic liability to SLE influences 5 blood cell perturbation responses, primarily attenuating neutrophil, monocyte, and white blood cell reactivity. These findings suggest that dysregulated functional responses in key immune cells may act as upstream drivers in SLE pathogenesis, while SLE genetic risk also feeds back to alter cellular behavior, highlighting potential biomarkers and therapeutic targets for SLE prevention and treatment.
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