Association between red blood cell distribution width and genetic risk in patients with rheumatoid arthritis: a prospective cohort study and Mendelian randomization analysis
Abstract Objective Elevated red blood cell distribution width (RDW) is associated with increased risk of rheumatoid arthritis (RA), but the potential interactions of RDW with genetic risk of incident RA remain unclear. This study aimed to investigate the associations between RDW, genetics, and the r...
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BMC
2025-01-01
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| Series: | BMC Rheumatology |
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| Online Access: | https://doi.org/10.1186/s41927-024-00451-1 |
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| author | Mingyang Chen Jing Lei Zhenqiu Liu Renjia Zhao Yanfeng Jiang Kelin Xu Tiejun Zhang Chen Suo Xingdong Chen |
| author_facet | Mingyang Chen Jing Lei Zhenqiu Liu Renjia Zhao Yanfeng Jiang Kelin Xu Tiejun Zhang Chen Suo Xingdong Chen |
| author_sort | Mingyang Chen |
| collection | DOAJ |
| description | Abstract Objective Elevated red blood cell distribution width (RDW) is associated with increased risk of rheumatoid arthritis (RA), but the potential interactions of RDW with genetic risk of incident RA remain unclear. This study aimed to investigate the associations between RDW, genetics, and the risk of developing RA. Methods We analysed data from 145,025 healthy participants at baseline in the UK Biobank. The endpoint was diagnosed rheumatoid arthritis (ICD-10 codes M05 and M06). Using previously reported results, we constructed a polygenic risk score for RA to evaluate the joint effects of RDW and RA-related genetic risk. Two-sample mendelian randomization and bayesian colocalization were used to infer the causal relation between them. Results A total of 675 patients with RA were enrolled and had a median followed up of 5.1 years, with an incidence rate of 0.57/1000 person-years. The hazard ratio of RA was 1.89 (95% CI: 1.45, 2.47) in highest RDW quartile group compared with the lowest RDW quartile group. Individuals within the top quintile of PRS showed a significantly high risk of RA. Moreover, Participants with high genetic risk and those in highest RDW group exhibited a significantly elevated hazard ratio (7.67, 95% CI: 3.98, 14.81), as opposed to participants with low genetic risk and those in lowest RDW group. Interactions between PRS and RDW on the multiplicative and additive scale were observed. Mendelian randomization provided suggestive evidence of a bi-directional causal relationship between RDW and RA. Loci near IL6R, IL1RN, FADS1/FADS2, UBE2L3 and HELZ2 showed colocalization. Conclusion Increased RDW is associated with elevated risk of incident RA especially in the high genetic risk populations, but only suggestive evidence supports a causal relationship between them. |
| format | Article |
| id | doaj-art-d99843b2c14f4bc3860a146626743351 |
| institution | Kabale University |
| issn | 2520-1026 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Rheumatology |
| spelling | doaj-art-d99843b2c14f4bc3860a1466267433512025-01-05T12:49:41ZengBMCBMC Rheumatology2520-10262025-01-019111010.1186/s41927-024-00451-1Association between red blood cell distribution width and genetic risk in patients with rheumatoid arthritis: a prospective cohort study and Mendelian randomization analysisMingyang Chen0Jing Lei1Zhenqiu Liu2Renjia Zhao3Yanfeng Jiang4Kelin Xu5Tiejun Zhang6Chen Suo7Xingdong Chen8State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and School of Life Science, Fudan UniversityDepartment of Epidemiology, School of Public Health, Fudan UniversityState Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and School of Life Science, Fudan UniversityState Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and School of Life Science, Fudan UniversityState Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and School of Life Science, Fudan UniversityDepartment of Epidemiology, School of Public Health, Fudan UniversityDepartment of Epidemiology, School of Public Health, Fudan UniversityDepartment of Epidemiology, School of Public Health, Fudan UniversityState Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and School of Life Science, Fudan UniversityAbstract Objective Elevated red blood cell distribution width (RDW) is associated with increased risk of rheumatoid arthritis (RA), but the potential interactions of RDW with genetic risk of incident RA remain unclear. This study aimed to investigate the associations between RDW, genetics, and the risk of developing RA. Methods We analysed data from 145,025 healthy participants at baseline in the UK Biobank. The endpoint was diagnosed rheumatoid arthritis (ICD-10 codes M05 and M06). Using previously reported results, we constructed a polygenic risk score for RA to evaluate the joint effects of RDW and RA-related genetic risk. Two-sample mendelian randomization and bayesian colocalization were used to infer the causal relation between them. Results A total of 675 patients with RA were enrolled and had a median followed up of 5.1 years, with an incidence rate of 0.57/1000 person-years. The hazard ratio of RA was 1.89 (95% CI: 1.45, 2.47) in highest RDW quartile group compared with the lowest RDW quartile group. Individuals within the top quintile of PRS showed a significantly high risk of RA. Moreover, Participants with high genetic risk and those in highest RDW group exhibited a significantly elevated hazard ratio (7.67, 95% CI: 3.98, 14.81), as opposed to participants with low genetic risk and those in lowest RDW group. Interactions between PRS and RDW on the multiplicative and additive scale were observed. Mendelian randomization provided suggestive evidence of a bi-directional causal relationship between RDW and RA. Loci near IL6R, IL1RN, FADS1/FADS2, UBE2L3 and HELZ2 showed colocalization. Conclusion Increased RDW is associated with elevated risk of incident RA especially in the high genetic risk populations, but only suggestive evidence supports a causal relationship between them.https://doi.org/10.1186/s41927-024-00451-1Rheumatoid arthritisRed blood cell distribution widthGenetic riskMendelian randomizationColocalization |
| spellingShingle | Mingyang Chen Jing Lei Zhenqiu Liu Renjia Zhao Yanfeng Jiang Kelin Xu Tiejun Zhang Chen Suo Xingdong Chen Association between red blood cell distribution width and genetic risk in patients with rheumatoid arthritis: a prospective cohort study and Mendelian randomization analysis BMC Rheumatology Rheumatoid arthritis Red blood cell distribution width Genetic risk Mendelian randomization Colocalization |
| title | Association between red blood cell distribution width and genetic risk in patients with rheumatoid arthritis: a prospective cohort study and Mendelian randomization analysis |
| title_full | Association between red blood cell distribution width and genetic risk in patients with rheumatoid arthritis: a prospective cohort study and Mendelian randomization analysis |
| title_fullStr | Association between red blood cell distribution width and genetic risk in patients with rheumatoid arthritis: a prospective cohort study and Mendelian randomization analysis |
| title_full_unstemmed | Association between red blood cell distribution width and genetic risk in patients with rheumatoid arthritis: a prospective cohort study and Mendelian randomization analysis |
| title_short | Association between red blood cell distribution width and genetic risk in patients with rheumatoid arthritis: a prospective cohort study and Mendelian randomization analysis |
| title_sort | association between red blood cell distribution width and genetic risk in patients with rheumatoid arthritis a prospective cohort study and mendelian randomization analysis |
| topic | Rheumatoid arthritis Red blood cell distribution width Genetic risk Mendelian randomization Colocalization |
| url | https://doi.org/10.1186/s41927-024-00451-1 |
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