Genetic variants and the risk of renal impairment in decompensated cirrhosis: a multi-ancestry genome-wide association study.

Genetic variant rs2099161 at the SUSD1 locus is significantly associated with renal impairment in decompensated cirrhosis, with a combined p-value of 8.31×10^-11.

• Why it matters: Understanding genetic susceptibility to renal impairment in cirrhosis can improve risk prediction and targeted interventions, addressing a major cause of mortality in these patients.
• What they did: A multi-ancestry GWAS involving over 3,200 patients identified the SUSD1 locus, with replication in additional cohorts, and transcriptomic analyses linked the variant to plasmacytoid dendritic cell activity and interferon signaling.
• The result: The rs2099161(C) risk allele increases kidney failure risk, especially in CC homozygotes, and highlights the plasmacytoid dendritic cell-interferon axis as a potential mechanism, enabling new therapeutic strategies.