Two-sample Mendelian randomization identified significant causal relationships between CD40L receptor levels (risk factor) and fibroblast growth factor 21 levels (protective factor) with endocarditis, suggesting they may serve as potential biomarkers and offer directions for targeted interventions.
Key Findings
Results
CD40L receptor levels were identified as a potential risk factor for endocarditis using the inverse variance weighted method.
OR = 1.258 (95% CI: 1.040–1.522, P = .018) by inverse variance weighted method
Single-nucleotide polymorphisms were used as instrumental variables
GWAS summary data for endocarditis were derived from the UK Biobank
GWAS data for 91 inflammatory proteins were from European-ancestry cohorts
MR-Steiger was used to confirm directionality of the causal relationship
Results
Fibroblast growth factor 21 (FGF21) levels were identified as a protective factor against endocarditis using the inverse variance weighted method.
OR = 0.689 (95% CI: 0.494–0.962, P = .029) by inverse variance weighted method
Bayesian-weighted analysis further supported this causal relationship
Weighted median and MR-Egger methods were applied as complementary approaches to validate the causal effect
The protective association suggests lower risk of endocarditis with higher FGF21 levels
Results
Sensitivity analyses showed no significant heterogeneity or horizontal pleiotropy for the identified causal associations.
No significant heterogeneity was detected by Cochran's Q test (P > .05)
MR-Egger intercept test did not indicate horizontal pleiotropy (P > .05)
MR-PRESSO global test did not indicate horizontal pleiotropy (P > .05)
Bayesian-weighted analysis further supported the causal relationships identified by inverse variance weighted
Methods
A 2-sample Mendelian randomization framework was applied to investigate causal relationships between 91 circulating inflammatory proteins and endocarditis.
Inverse variance weighted method was the primary analytic approach
Weighted median, MR-Egger, and Bayesian-weighted methods were applied as complementary approaches
MR-Steiger was used to evaluate directionality of causal effects
GWAS data for 91 inflammatory proteins were sourced from European-ancestry cohorts
Of 91 proteins tested, 2 showed statistically significant causal associations with endocarditis
Jiang X, Guan Y, Chen C, Wu X. (2026). Revealing causal associations of 91 inflammatory protein factors with endocarditis: Insights from genome-wide association study.. Medicine. https://doi.org/10.1097/MD.0000000000048141