CR1 variants contribute to FSGS susceptibility across multiple populations

Focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome, with an annual incidence of 24 cases per million among African-Americans and 5 per million among European-Americans in the United States. It ranks as the second most common glomerular disease in Europe and Latin America and the fifth in Asia. We conducted a case-control study involving 726 FSGS cases and 13,994 controls from diverse ethnic backgrounds, using panel sequencing of ∼2,500 podocyte-expressed genes. Rare variant association tests confirmed known risk genes (<i>KANK1</i>, <i>COLAPOL1</i>) and identified a significant association with the <i>CR1</i> gene. The <i>CR1</i> variant rs17047661, which encodes the Sl1/Sl2 (R1601G) allele, was previously linked to cerebral malaria protection and is now identified as a risk variant for FSGS. This highlights an evolutionary trade-off between infectious disease resistance and kidney disease susceptibility, emphasizing the role of adaptive immunity in FSGS pathogenesis and potential therapeutic targets.

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Publication Details

Journal
iScience
Published
2025-03-18
DOI
https://doi.org/10.1016/j.isci.2025.112234
Citations
1
Primary Topic
Immunodeficiency and Autoimmune Disorders
Type
article
Field-Weighted Citation Impact
0.80
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article

CR1 variants contribute to FSGS susceptibility across multiple populations

Cheryl Ann Winkler, Christine Stevens, Rostislav Skitchenko, Alexey Sergushichev et al.
1 citations
iScience
Immunodeficiency and Autoimmune Disorders
0.80
article

CR1 variants contribute to FSGS susceptibility across multiple populations

Cheryl Ann Winkler, Christine Stevens, Rostislav Skitchenko, Alexey Sergushichev, Jeffrey B. Kopp, Zora Modrušan, Mykyta Artomov, Alexander A. Loboda, Andréy S. Shaw, Namrata Gupta, Mark J. Daly
article en
1 citations

Abstract

Focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome, with an annual incidence of 24 cases per million among African-Americans and 5 per million among European-Americans in the United States. It ranks as the second most common glomerular disease in Europe and Latin America and the fifth in Asia. We conducted a case-control study involving 726 FSGS cases and 13,994 controls from diverse ethnic backgrounds, using panel sequencing of ∼2,500 podocyte-expressed genes. Rare variant association tests confirmed known risk genes (<i>KANK1</i>, <i>COLAPOL1</i>) and identified a significant association with the <i>CR1</i> gene. The <i>CR1</i> variant rs17047661, which encodes the Sl1/Sl2 (R1601G) allele, was previously linked to cerebral malaria protection and is now identified as a risk variant for FSGS. This highlights an evolutionary trade-off between infectious disease resistance and kidney disease susceptibility, emphasizing the role of adaptive immunity in FSGS pathogenesis and potential therapeutic targets.

iScienceVol. 28(4)
Broad Institute (US), Nationwide Children's Hospital (US), ITMO University (RU), Federal Almazov North-West Medical Research Centre (RU), Massachusetts General Hospital (US), National Institute of Diabetes and Digestive and Kidney Diseases (US), Frederick National Laboratory for Cancer Research (US), Institute for Molecular Medicine Finland (FI), National Cancer Institute (US), The Ohio State University (US)
Zero hunger
Openalex Percentile: Top 30%
Immunodeficiency and Autoimmune Disorders
0.80
DOIOpen Access PDFOpenAlex
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