Trans-ethnic Mendelian randomization analysis of membranous nephropathy and peripheral artery disease with mediating effects of thrombomodulin.

ABSTRACT: This study employed a trans-ethnic two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between membranous nephropathy (MN) and peripheral artery disease (PAD). In European populations, MN exhibited a significant positive causal effect on PAD (discovery: OR = 1.040, P = 0.028; validation: OR = 1.028, P = 0.031), whereas no such association was observed in East Asians (P > 0.05). A two-step mediation analysis identified several proteins influenced by MN, including thrombomodulin (TM) (β = 0.031, P = 0.001), macrophage colony-stimulating factor 1 (MCSF1) (β = 0.239, P = 0.015), stem cell factor (SCF) (β = 0.028, P = 0.002), and tissue factor (TF) (β = 0.031, P = 0.001), while MN negatively affected interleukin-1β (IL-1β) (β=-0.049, P = 0.015) and hepatocyte

SUBMITTER: Pan J 

PROVIDER: S-EPMC12098656 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature