Home›Hematology› Local ancestry-aware GWAS finds 38 European-tract and 12 African-tract loci for eGFR in sickle cell disease
Local ancestry-aware GWAS finds 38 European-tract and 12 African-tract loci for eGFR in sickle cell diseaseNew genetic markers may help identify kidney damage in sickle cell disease
Blood advancesPublished October 27, 2026Study authors: Garrett Melanie E, Nouraie Seyed Mehdi, Machado Roberto F, Gordeuk Victor R, Gladwin Mark T, Telen M…PubMed ↗DOI ↗Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease
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Key Takeaway
Recognize these eGFR loci as associational and hypothesis-generating, not yet clinically actionable.
This is a genome-wide association study meta-analysis applying local ancestry-aware methods to estimated glomerular filtration rate (eGFR) in adults with sickle cell disease (SCD). The approach partitions genetic signal by ancestry tract rather than treating ancestry as a single covariate.
The authors report 12 significant genomic regions within the African ancestry tract and 38 significant regions within the European ancestry tract. Effect sizes, p-values or confidence intervals, and the direction of associations were not reported in the available summary, so the magnitude and consistency of these signals cannot be judged from this source.
Sample size, setting, and follow-up were not reported, and the authors' stated limitations were not available. The analysis is explicitly associational; no causal inference about kidney dysfunction is supported. Safety data are not applicable to this design.
The authors propose that the identified regions represent new targets that could be useful for early identification and treatment of kidney dysfunction in patients with SCD. That is a hypothesis-generating claim: the loci have not been validated in independent cohorts, functionally characterized, or tested for clinical utility in this report.
Practice relevance is therefore indirect. These findings do not change current screening or management of sickle cell nephropathy, but they may inform future work on genetic risk stratification if replicated and translated.
How this fits prior evidence
Prior coverage has focused on genetic and clinical modifiers in SCD, including 40 independent loci associated with acute chest syndrome. This meta-analysis extends that genetic line of inquiry to kidney function, reporting 12 African-tract and 38 European-tract regions for eGFR, and it adds an ancestry-aware analytic approach not reflected in earlier coverage. It contrasts with the therapeutic focus of prior items, such as mitapivat improving haemoglobin without significantly reducing pain frequency, and with transfusion-safety and alloimmunization findings, which address care delivery rather than genomics. No prior item addressed sickle cell nephropathy genetics.
Living with sickle cell disease can put a heavy strain on the body, especially the kidneys. Over time, this can lead to kidney dysfunction, a condition where the kidneys struggle to filter waste from the blood. Identifying the genetic roots of this problem is a major step toward better care.
By looking at the genetic makeup of patients, researchers identified several specific regions linked to kidney health. They found 12 significant regions in the African tract and 38 significant regions in the European tract. These areas are linked to the glomerular filtration rate, which is a measure of how well the kidneys are working.
While these findings are still early, they offer a roadmap for the future. These genetic markers could eventually help doctors identify kidney problems sooner. This could lead to earlier treatments and better long-term outcomes for people managing sickle cell disease.
What this means for you:
New genetic markers could help doctors identify and treat kidney damage in sickle cell disease patients earlier.
Common questions
What did the study find about sickle cell disease and kidneys?
The study identified specific genomic regions that are linked to kidney function in adults with sickle cell disease. Specifically, researchers found 12 significant regions in the African tract and 38 significant regions in the European tract. These areas are linked to the glomerular filtration rate, which measures how well the kidneys filter waste.
How can these genetic findings help patients?
These findings suggest new targets that could help doctors identify kidney dysfunction earlier. By spotting these issues sooner, medical teams may be able to start treatments sooner for patients with sickle cell disease who are at risk of kidney damage.
In the United States, sickle cell disease (SCD) is a rare inherited hemoglobinopathy affecting ∼100 000 individuals, mostly with African ancestry. SCD causes damage to multiple organ systems, and SCD nephropathy (SCDN) is a common complication associated with early mortality. We previously performed a genome-wide association study (GWAS) for SCDN and identified a modest number of genome-wide significant loci. Here, we leveraged the ancestral composition of participants from 2 well-characterized adult SCD cohorts to boost statistical power and perform a local ancestry-aware GWAS for estimated glomerular filtration rate, resulting in the identification of novel genome-wide significant loci within the African and European ancestral components of participants. Meta-analysis identified 12 significant genomic regions in the African tract, including peptidylprolyl isomerase like 6, ARHGAP24, RAB11A, and STEAP3, and 38 regions in the European tract, including UBLCP1, a disintegrin and metalloproteinase with thrombospondin motifs 6, JAZF1, MYO7B, MYO1C, PDGFA, GPC5, LRP1B, KANK1, and TRPV5. The identified regions encompass genes affecting inflammation, extracellular matrix integrity, iron metabolism, magnesium ion homeostasis, B-cell apoptosis, tumor necrosis factor production, and estrogen signaling. Many of these genes and pathways are important not only for renal function but also for SCD biology, providing additional support for the hypothesis that SCDN pathophysiology is unique from other forms of kidney disease. This study represents the largest local ancestry-aware analysis of SCDN to date, furthers our understanding of the genetic risk factors underlying SCDN, and proposes new targets that could be useful for the early identification and treatment of kidney dysfunction in patients with SCD.
