Elevated homocysteine contributes to the progression of type 1 diabetic nephropathy: Evidence from Mendelian randomization and experimental validation.

ABSTRACT: Hyperhomocysteinemia has been identified as a potential metabolic risk factor for type 1 diabetes-related nephropathy (T1DN). However, the causal relationship between homocysteine (Hcy) and T1DN remains unclear. We performed univariable Mendelian randomization (MR) and multivariable MR analyses to investigate the causal effects of Hcy and B vitamins (vitamin B6, B12, and folate) on T1DN in a cohort of 19,406 individuals. Linkage disequilibrium score regression and colocalization analyses were conducted to examine genetic correlations. Additionally, 2-step MR analysis was employed to identify potential mediating factors. Our MR findings revealed that elevated Hcy levels were causally associated with the late stage of T1DN (OR = 1.33, 95% CI: 1.08-1.64; P < .0001; false discovery rate < 0.05

SUBMITTER: He M 

PROVIDER: S-EPMC12863804 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature