7-OR: Causal Associations between Glyoxalase 1 Expression and Kidney Disease in Type 1 Diabetes

摘要: Methods: The potential causality between GLO1 and DKD was analyzed by two-sample MR. As instrumental variables (IV) we selected cis-expression quantitative trait loci (eQTL) independently associated with GLO1 expression (r 2< 0.01) in blood, kidney, and other tissues from publicly available datasets (blood: eQTLGen, kidney tissue: Human Kidney eQTL atlas, other tissues: GTEx v8). Serum protein expression data were retrieved from genome-wide association study (GWAS) Catalogue (Study accession: GCST90090884). DKD outcome data were retrieved from JDRF-DNCRI GWAS on DKD, including 19406 individuals with type 1 diabetes, with spectrum of ten DKD definitions based on albuminuria and kidney function.Results: MR suggested that higher GLO1 mRNA expression (eQTL threshold p< 5.0 x10-8) in skin (OR 0.86,[95% CI 0.77-0.97], p= 0.01, three SNPs) and salivary gland (OR 0.83,[95% CI 0.72-0 …