The causal associations of inflammatory cytokines with obesity and systemic lupus erythematosus: A Mendelian randomization study.
Int J Rheum Dis
; 27(6): e15214, 2024 Jun.
Article
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| MEDLINE
| ID: mdl-38831532
ABSTRACT
OBJECTIVE:
Previous studies have partly discussed the roles of inflammatory cytokines in obesity and systemic lupus erythematosus (SLE), but the causal relationship among inflammatory cytokines, obesity, and SLE is unclear. It is challenging to comprehensively evaluate the causal relationship between these variables. This study aimed to investigate the role of cytokines as intermediates between obesity and SLE.METHODS:
The inverse-variance weighted method (IVW) of mendelian randomization (MR) is mainly used to explore the causal relationship between exposure and outcome by using the genetic variation of the open large genome-wide association studies (GWAS), namely single-nucleotide polymorphisms (SNPs) related to obesity (more than 600 000 participants), inflammatory cytokines (8293 healthy participants) and SLE (7219 cases). Methods such as weighted median, MR-Egger are used to evaluate the reliability of causality. Reverse analysis is performed for each MR analysis to avoid reverse causality. Cochran's Q statistic and funnel chart are used to detect heterogeneity, MR-Egger intercept test and leave-one-out sensitivity analyses evaluated pleiotropy.RESULTS:
Obesity was associated with 25 cytokines, and 3 cytokines were associated with SLE, including CTACK (OR = 1.19, 95% CI 1.06, 1.33, p = .002), IL-18 (OR = 1.13, 95% CI 1.01, 1.26, p = .027), SCGFb (OR = 0.89, 95% CI 0.79, 0.99, p = .044). In the opposite direction, SLE was associated with 18 cytokines, and 2 cytokines were associated with obesity, including IP-10 (ßIVW = -.03, 95% CI -0.05, -0.01, p = .002), MIP-1B (ßIVW = -.03, 95% CI -0.05, -0.01, p = .004).CONCLUSION:
Our MR study suggested that CTACK, IL-18 and SCGFb may play an intermediary role in obesity to SLE, while IP-10 and MIP-1B may play an intermediary role in SLE to obesity.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Citocinas
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Polimorfismo de Nucleótido Simple
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Estudio de Asociación del Genoma Completo
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Análisis de la Aleatorización Mendeliana
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Lupus Eritematoso Sistémico
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Obesidad
Límite:
Humans
Idioma:
En
Revista:
Int J Rheum Dis
Asunto de la revista:
REUMATOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China