Genetic prediction of blood cell reactivity and its potential causal influence on bone continuity and density disordersOA
Background:This study aimed to investigate the potential causal relationship be-tween genetically predicted human blood cell(HBC)reactivity and disorders of bone continuity,density,and structure.Methods:We analyzed summary-level GWAS data for 91 HBC traits and two bone-related outcomes from publicly available sources,employing the inverse-variance weighted(IVW)method as the principal Mendelian randomization(MR)technique.The sensitivity analyses comprised MR-Egger regression and MR-PRESSO.Results:MR analysis identified suggestive associations between red blood cell(RBC)perturbation response(Pam3CSK4),neutrophil perturbation response(side fluores-cence coefficient of variation of neutrophil 4),Neutrophil perturbation response(col-chicine),Monocyte perturbation response(TMAO perturbation)and bone continuity.The MR results are:[β:−0.13,odds ratio(OR):0.88;95%confidence interval(CI):0.77,0.99;p=0.040],[β:0.11,OR:1.12,95%CI:1.02,1.23;p=0.016],[β:−0.11,OR:0.90,95%CI:0.81,0.99;p=0.029]and[β:−0.04,OR:0.96,95%CI:0.92,0.99;p=0.023].In addition,Neutrophil perturbation response(forward scatter median of neutrophil 1),Unknown cell population perturbation response(nigericin)and other disorders of bone density and structure are also potential causal factors,with MR Result[β:0.21,OR:1.24,95%CI:1.01,1.51;p=0.034],[β:0.03,OR:1.03,95%CI:1.00,1.06;p=0.042].Reverse Mendelian randomization sensitivity analysis showed a potential bidirectional association between specific HBC features and bone-related outcomes.Conclusions:This exploratory study offer valuable preliminary insights into the blood cell functional reactivity and bone health.The findings,while requiring independent validation,highlight plausible biological pathways for further elucidation.
Zhiqin Deng;Zhe Zhao;Wenting Jiang;Xiaoqiang Chen;Jianquan Liu;Xu Tao;Zhengyang Lin;Zhenhan Deng;Wencui Li
Hand and Foot Surgery Department,Shenzhen Second People''s Hospital/The First Hospital Affiliated to Shenzhen University,Medical Innovation Technology Transformation Center of Shenzhen Second People''s Hospital,Shenzhen,ChinaHand and Foot Surgery Department,Shenzhen Second People''s Hospital/The First Hospital Affiliated to Shenzhen University,Medical Innovation Technology Transformation Center of Shenzhen Second People''s Hospital,Shenzhen,ChinaOperating Room,Shenzhen Second People''s Hospital/The First Hospital Affiliated to Shenzhen University,Shenzhen,ChinaHand and Foot Surgery Department,Shenzhen Second People''s Hospital/The First Hospital Affiliated to Shenzhen University,Medical Innovation Technology Transformation Center of Shenzhen Second People''s Hospital,Shenzhen,ChinaHand and Foot Surgery Department,Shenzhen Second People''s Hospital/The First Hospital Affiliated to Shenzhen University,Medical Innovation Technology Transformation Center of Shenzhen Second People''s Hospital,Shenzhen,ChinaHand and Foot Surgery Department,Shenzhen Second People''s Hospital/The First Hospital Affiliated to Shenzhen University,Medical Innovation Technology Transformation Center of Shenzhen Second People''s Hospital,Shenzhen,ChinaDepartment of Orthopedics,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China Geriatrics Center,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,ChinaDepartment of Orthopedics,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China Geriatrics Center,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,ChinaHand and Foot Surgery Department,Shenzhen Second People''s Hospital/The First Hospital Affiliated to Shenzhen University,Medical Innovation Technology Transformation Center of Shenzhen Second People''s Hospital,Shenzhen,China
医药卫生
disorders of bone continuitydisorders of bone density and structurehuman blood cellMendelian randomizationosteoporosis
《Animal Models and Experimental Medicine》 2026 (5)
P.932-946,15
National Natural Science Foundation of China,Grant/Award Number:81800785,81972085 and 82172465the Natural Science Foundation of Guangdong Province,Grant/Award Number:2023A1515010102,2024A1515220060Guangdong Provincial Key Clinical Discipline-Orthopedics,Grant/Award Number:2000005Guangdong Province Medical Science and Technology Research Foundation Project,Grant/Award Number:A2024359the Sanming Project of Shenzhen Health and Family Planning Commission,Grant/Award Number:SZSM202311008Shenzhen Science and Technology Planning,JCYJ20240813141011015,JCYJ20250604180734044 and JCYJ20250604180551064the Municipal Financial Subsidy of Shenzhen Medical。
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