Identification of circulating inflammatory proteins as potential drug targets for sepsis through Mendelian randomization and colocalization analyses.

ABSTRACT: Sepsis is a complex disease with limited therapeutics. We conducted a 2-sample Mendelian randomization (MR) analysis to identify circulating inflammatory proteins as potential drug targets for sepsis. Protein quantitative trait loci (pQTLs) at cis-region for 448 circulating inflammatory proteins were obtained from the UK biobank pharma proteomics project (UKB-PPP) (N = 54219), and summary-level genetic associations with sepsis were extracted from the FinnGen cohort (12,301 cases and 332,343 controls) for the primary MR analysis. The findings were further replicated using alternative cis-pQTL (Fenland, N = 10708) and sepsis genome-wide association study data (UK Biobank, 2811 cases and 406,150 controls). Multiple sensitivity analyses including summary-data-based MR (SMR), the HEIDI test, co

SUBMITTER: Wan F 

PROVIDER: S-EPMC12582709 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature