Genetically predicted lower FLT3L levels increase the risk of hypertrophic cardiomyopathy partly mediated by phosphate: Evidence from a 2-step Mendelian randomization analysis.
Y, L., R, C., C, H., Z, Z., S, X., X, Z., M, L., X, L., M, B., & C, H. (2026). Genetically predicted lower FLT3L levels increase the risk of hypertrophic cardiomyopathy partly mediated by phosphate: Evidence from a 2-step Mendelian randomization analysis.. Medicine. https://doi.org/10.1097/MD.0000000000049477
Y L, R C, C H, Z Z, S X, X Z, et al. Genetically predicted lower FLT3L levels increase the risk of hypertrophic cardiomyopathy partly mediated by phosphate: Evidence from a 2-step Mendelian randomization analysis.. Medicine. 2026; doi: 10.1097/MD.0000000000049477
Y L, R C, C H, et al. Genetically predicted lower FLT3L levels increase the risk of hypertrophic cardiomyopathy partly mediated by phosphate: Evidence from a 2-step Mendelian randomization analysis.[J]. Medicine. 2026. DOI: 10.1097/MD.0000000000049477.
@article{y2026,
author = {Li Y and Chen R and Hou C and Zheng Z and Xu S and Zheng X and Liu M and Liao X and Bao M and Huang C},
title = {Genetically predicted lower FLT3L levels increase the risk of hypertrophic cardiomyopathy partly mediated by phosphate: Evidence from a 2-step Mendelian randomization analysis.},
journal = {Medicine},
year = {2026},
doi = {10.1097/MD.0000000000049477},
note = {PMID: 42363547},
}
TY - JOUR AU - Li Y AU - Chen R AU - Hou C AU - Zheng Z AU - Xu S AU - Zheng X AU - Liu M AU - Liao X AU - Bao M AU - Huang C TI - Genetically predicted lower FLT3L levels increase the risk of hypertrophic cardiomyopathy partly mediated by phosphate: Evidence from a 2-step Mendelian randomization analysis. T2 - Medicine PY - 2026 DO - 10.1097/MD.0000000000049477 AN - PMID:42363547 ER -
We performed a 2-step Mendelian randomization (MR) study to investigate the associations of Fms-related tyrosine kinase 3 ligand (FLT3L) and phosphate levels with the risk of hypertrophic cardiomyopathy (HCM). Genetic instruments for 75 circulating inflammatory factors were obtained from the NHGRI-EBI GWAS Catalog, while summary statistics for circulating phosphate and HCM were derived from the UK Biobank and FinnGen, respectively. Univariable MR analysis using the inverse-variance weighted method indicated that genetically predicted higher phosphate levels were associated with an increased risk of HCM (OR = 1.36, P = 4.82 × 10-2). Among the inflammatory markers, FLT3L emerged as a significant candidate and showed inverse associations with phosphate levels (β = -0.05, P = 1.70 × 10-9) and HCM (OR = 0.79, P = 4.10 × 10-2). Bidirectional MR analyses did not support a causal effect of phosphate on FLT3L. Mediation analysis suggested that phosphate levels accounted for an estimated 12.05% of the total effect of FLT3L on HCM. Genetic liability to lower FLT3L levels is associated with a higher risk of HCM, and this relationship may be partially mediated through circulating phosphate levels.