Evidence map›Paper›PMID 41748071›Full record

ArticleKidney international2026

Polygenic risk scores and HLA class II variants are biomarkers of corticosteroid response in childhood nephrotic syndrome.

Tiffany Tu, Alejandro Ochoa, Amika Sood, Ashley Dabrik, Megan Chryst-Stangl, Brandon Lane, Guanghong Wu, Frank Donovan, Ursula Harper, Settara Chandrasekharappa and 41 more

Abstract read
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Article in Kidney international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

51 authors.

Tiffany TuComputational Biology and Bioinformatics Program, Duke University, Durham, North Carolina, USA; Center for Statistical Genetics and Genomics, Duke University, Durham, North Carolina, USA.
Alejandro OchoaComputational Biology and Bioinformatics Program, Duke University, Durham, North Carolina, USA; Center for Statistical Genetics and Genomics, Duke University, Durham, North Carolina, USA; Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA.
Amika SoodCenter for Statistical Genetics and Genomics, Duke University, Durham, North Carolina, USA; Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA.
Ashley DabrikDepartment of Surgery and Immunology, Duke University School of Medicine, Durham, North Carolina, USA.
Megan Chryst-StanglDepartment of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Brandon LaneDepartment of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Guanghong WuDepartment of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Frank DonovanGenomics Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Ursula HarperGenomics Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Settara ChandrasekharappaGenomics Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Christopher EsezoborDepartment of Pediatrics, College of Medicine, University of Lagos, Lagos, Nigeria; Lagos University Teaching Hospital, Lagos, Nigeria.
Adaobi SolarinDepartment of Pediatrics, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.
David HooperDepartment of Pediatrics, Cincinnati Children's Hospital Medical, Cincinnati, Ohio, USA.
Christine SethnaDivision of Pediatric Nephrology, Cohen Children's Medical Center, New Hyde Park, New York, USA.
Sandra AmaralDivision of Nephrology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Mahmoud KallashDivision of Pediatric Nephrology, Nationwide Children's Hospital, Columbus, Ohio, USA.
Michelle RheaultDepartment of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Priya VergheseDepartment of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Vikas DharnidharkaDepartment of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
Eloise SalmonDepartment of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
Patricia WengDepartment of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Tarak SrivastavaChildren's Mercy Hospital, Kansas City, Missouri, USA; University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.
Michael E SeifertDepartment of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Cozumel PruetteDepartment of Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
David SelewskiDepartment of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA.
Keisha GibsonDepartment of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
Tracy HunleyDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Asiri AbeyagunawardenaDepartment of Pediatrics, University of Peradeniya, Peradeniya, Sri Lanka.
Shenal ThalgahagodaDepartment of Pediatrics, University of Peradeniya, Peradeniya, Sri Lanka.
Arvind BaggaDepartment of Pediatrics, Division of Nephrology, All India Institute of Medical Science, Ansari Nagar, New Delhi, India.
Aditi SinhaDepartment of Pediatrics, Division of Nephrology, All India Institute of Medical Science, Ansari Nagar, New Delhi, India.
Nicholas WebbDepartment of Pediatric Nephrology, University of Manchester, Manchester, UK.
Larry GreenbaumDepartment of Pediatrics, Division of Pediatric Nephrology, Emory University, Atlanta, Georgia; Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Ali GharaviDepartment of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Krzysztof KirylukDepartment of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Matthias KretzlerDepartment of Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.
Lisa Guay-WoodfordResearch Institute, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Simone Sanna-CherchiDepartment of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Agnieszka BierzynskaDepartment of Pediatric Nephrology, Bristol Royal Hospital for Children, University Hospitals Bristol, Bristol, UK; Weston NHS Foundation Trust, Bristol, UK.
Ania KoziellDepartment of Pediatric Nephrology, Evelina Children's Hospital, London, UK.
Gavin WelshDepartment of Pediatric Nephrology, Bristol Royal Hospital for Children, University Hospitals Bristol, Bristol, UK; Weston NHS Foundation Trust, Bristol, UK.
Moin SaleemDepartment of Pediatric Nephrology, Bristol Royal Hospital for Children, University Hospitals Bristol, Bristol, UK; Weston NHS Foundation Trust, Bristol, UK.
Charles RotimiCenter for Research for Genomics and Global Health, National Human Genome Research Institute, Bethesda, Maryland, USA.
Eileen ChambersDepartment of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Cliburn ChanComputational Biology and Bioinformatics Program, Duke University, Durham, North Carolina, USA; Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA.
CureGN Consortium
PNRC Glomerular Disease Group
CIBMTR/NMDP Consortium
Annette JacksonDepartment of Surgery and Immunology, Duke University School of Medicine, Durham, North Carolina, USA.
Adebowale AdeyemoCenter for Research for Genomics and Global Health, National Human Genome Research Institute, Bethesda, Maryland, USA.
Rasheed GbadegesinDepartment of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA. Electronic address: rasheed.gbadegesin@duke.edu.

Funding

New York Center for Collaborative Research In Common Disease Genomics: Genome Aggregation and Joint Variant Calling for CCDG Freeze2UM1HG008901 · NHGRI · NEW YORK GENOME CENTER · PI MANIATIS, THOMAS P, WIGLER, MICHAEL H · 2016 to 2020
$56.6M
Genetic epidemiology of complex diseasesZIAHG200362 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI ROTIMI, CHARLES · 2009 to 2025
$54.7M
CureGNU24DK100845 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CRYSTAL A. GADEGBEKU, Laura H Mariani · 2019 to 2026
$12.1M
CureGN-Penn PCCU01DK100846 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI LAWRENCE B. HOLZMAN · 2019 to 2026
$8.3M
CUREGN 3.0 - Pediatric Nephrology Consortium - PCCU01DK100866 · NIDDK · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI Laurence A Greenbaum, Jon Klein · 2019 to 2026
$7.7M
Integrating large scale genomics and functional studies to accelerate FSGS/NS discoveryRC2DK122397 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI HILDEBRANDT, FRIEDHELM, POLLAK, MARTIN R. · 2020 to 2024
$7.4M
CureGN-3: UNCPCCU01DK100867 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Vimal Kumar Derebail, Ronald J Falk · 2019 to 2026
$6.7M
Defining the Landscape of HLA Risk Alleles in Primary Nephrotic Syndrome and Post Kidney Transplant RecurrenceU01AI152585 · NIAID · DUKE UNIVERSITY · PI GBADEGESIN, RASHEED ADEBAYO, JACKSON, ANNETTE MARIE · 2020 to 2024
$3.7M
Intramural NIH HHS ZIA HG200362NHGRI NIH HHS UM1 HG008901NIAID NIH HHS U01 AI152585NIDDK NIH HHS RC2 DK122397NIDDK NIH HHS U01 DK100846NIDDK NIH HHS U01 DK100866NIDDK NIH HHS U01 DK100867NIDDK NIH HHS U24 DK100845
6 · The paper itself

Abstract

introductionNephrotic syndrome (NS), a common glomerular disease in children, is classified based on response to corticosteroid therapy as either steroid-sensitive nephrotic syndrome (SSNS), or steroid-resistant nephrotic syndrome (SRNS). However, there are no current reliable predictors of therapy response at initial clinical presentation.

methodsTo evaluate predictors, we conducted genome-wide association studies, developed polygenic risk scores (PRS) for therapy response and analyzed classical HLA alleles in 1,997 children (994 discovery and 1,003 replication/validation cohorts) previously unstudied children with NS and 3,558 ancestry-matched control individuals.

resultsA significant association with HLA loci defined by variants in HLA-DQB1, HLA-DRB1, and HLA-DQA1 were found for SSNS (but not SRNS), along with a second immune-related SSNS locus: CLEC16A. A PRS that discriminates between SSNS and SRNS was validated in two independent cohorts. The HLA haplotype HLA- DRB1∗07:01∼DQA1∗02:01∼DQB1∗02:02 was associated with about four times the risk of developing SSNS. A model incorporating HLA haplotype, PRS score, and age at disease onset was the best predictor of steroid responsiveness with an area under the curve of 0.68-0.70 and an overall classification accuracy of SSNS versus SRNS of 67-71%.

conclusionsOur findings confirm that SSNS, unlike SRNS, is an immune-mediated HLA-associated disorder. The PRS for therapy response and HLA haplotype can serve as biomarkers, provide a foundation for more accurate diagnoses and tailored individualized treatment.

Indexed as

Adrenal Cortex HormonesGenetic Risk ScoreHLA-DRB1 ChainsNephrotic SyndromeAdolescentBiomarkersCase-Control StudiesChildChild, PreschoolDrug ResistanceFemaleGenome-Wide Association StudyHaplotypesHLA-DQ alpha-ChainsHLA-DQ beta-ChainsHumansAdrenal Cortex HormonesBiomarkersHLA-DQA1 antigenHLA-DQ alpha-ChainsHLA-DQB1 antigenHLA-DQ beta-ChainsHLA-DRB1 ChainsHLA haplotypenephrotic syndromepolygenic risk scoretherapy response

Identifiers

PMID41748071
PMCPMC13065301

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.