A single genetic locus controls both expression of DPEP1/CHMP1A and kidney disease development via ferroptosis

• DOI: 10.1038/s41467-021-25377-x
• Publication Date: 2021-08-23T10:49:01Z
• Authors: Yuting Guan; Xiujie Liang; Ziyuan Ma; Hailong Hu; Hongbo Liu; Zhen Miao; Andreas Linkermann; Jacklyn N. Hellwege; Benjamin F. Voight; Katalin Susztak
• Keywords: Genome-wide Association Study

Abstract Genome-wide association studies (GWAS) have identified loci for kidney disease, but the causal variants, genes, and pathways remain unknown. Here we identify two disease genes Dipeptidase 1 ( DPEP1 ) Charged Multivesicular Body Protein A CHMP1A via triangulation of function GWAS, human expression, methylation quantitative trait loci. Using single-cell chromatin accessibility genome editing, fine map region that controls expression both genes. Mouse genetic models demonstrate roles in disease. Cellular indicate Dpep1 Chmp1a are important regulators a single pathway, ferroptosis lead to development altering cellular iron trafficking.