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

Yuting Guan; Xiujie Liang; Ziyuan Ma; Hailong Hu; Hongbo Liu; Zhen Miao; Andreas Linkermann; Jacklyn N. Hellwege; Benjamin F. Voight; Katalin Susztak

doi:10.1038/s41467-021-25377-x

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

Yuting Guan, Xiujie Liang, Ziyuan Ma, Hailong Hu, Hongbo Liu, Zhen Miao, Andreas Linkermann, Jacklyn N. Hellwege, Benjamin F. Voight, Katalin Susztak

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

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

Original language	English
Article number	5078
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-25377-x
State	Published - 1 Dec 2021
Externally published	Yes

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

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

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doi = "10.1038/s41467-021-25377-x",

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AU - Guan, Yuting

AU - Liang, Xiujie

AU - Ma, Ziyuan

AU - Hu, Hailong

AU - Liu, Hongbo

AU - Miao, Zhen

AU - Linkermann, Andreas

AU - Hellwege, Jacklyn N.

AU - Voight, Benjamin F.

AU - Susztak, Katalin

PY - 2021/12/1

Y1 - 2021/12/1

N2 - Genome-wide association studies (GWAS) have identified loci for kidney disease, but the causal variants, genes, and pathways remain unknown. Here we identify two kidney disease genes Dipeptidase 1 (DPEP1) and Charged Multivesicular Body Protein 1 A (CHMP1A) via the triangulation of kidney function GWAS, human kidney expression, and methylation quantitative trait loci. Using single-cell chromatin accessibility and genome editing, we fine map the region that controls the expression of both genes. Mouse genetic models demonstrate the causal roles of both genes in kidney disease. Cellular studies indicate that both Dpep1 and Chmp1a are important regulators of a single pathway, ferroptosis and lead to kidney disease development via altering cellular iron trafficking.

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

UR - https://www.scopus.com/pages/publications/85113307849

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DO - 10.1038/s41467-021-25377-x

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

Abstract

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