Genome-wide polygenic score to predict chronic kidney disease across ancestries.

Apolipoprotein L1 / genetics Genetic Predisposition to Disease / genetics Genome-Wide Association Study Genotype Humans Multifactorial Inheritance / genetics Polymorphism, Single Nucleotide / genetics Renal Insufficiency, Chronic / diagnosis

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
07 2022
Historique:
received: 09 11 2021
accepted: 11 05 2022
pubmed: 18 6 2022
medline: 27 7 2022
entrez: 17 6 2022
Statut: ppublish

Résumé

Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality. Polygenic prediction could enhance CKD screening and prevention; however, this approach has not been optimized for ancestrally diverse populations. By combining APOL1 risk genotypes with genome-wide association studies (GWAS) of kidney function, we designed, optimized and validated a genome-wide polygenic score (GPS) for CKD. The new GPS was tested in 15 independent cohorts, including 3 cohorts of European ancestry (n = 97,050), 6 cohorts of African ancestry (n = 14,544), 4 cohorts of Asian ancestry (n = 8,625) and 2 admixed Latinx cohorts (n = 3,625). We demonstrated score transferability with reproducible performance across all tested cohorts. The top 2% of the GPS was associated with nearly threefold increased risk of CKD across ancestries. In African ancestry cohorts, the APOL1 risk genotype and polygenic component of the GPS had additive effects on the risk of CKD.

Identifiants

DOI: 10.1038/s41591-022-01869-1 PMID: 35710995 PMC: PMC9329233
pubmed: 35710995
doi: 10.1038/s41591-022-01869-1
pii: 10.1038/s41591-022-01869-1
pmc: PMC9329233
mid: NIHMS1811979
doi:

Substances chimiques

APOL1 protein, human 0
Apolipoprotein L1 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1412-1420

Subventions

Organisme : NIDDK NIH HHS
ID : F31 DK128990
Pays : United States
Organisme : NIA NIH HHS
ID : R00 AG054573
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG011167
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK116672
Pays : United States
Organisme : NIDDK NIH HHS
ID : K23 DK116967
Pays : United States
Organisme : NIDDK NIH HHS
ID : K25 DK128563
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136666
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM140487
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK078616
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD043483
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008685
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008680
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL155466
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Atlas Khan (A)

Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
ORCID: 0000-0002-6651-2725

Michael C Turchin (MC)

Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0003-3569-1529

Amit Patki (A)

Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.

Vinodh Srinivasasainagendra (V)

Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.

Ning Shang (N)

Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
ORCID: 0000-0001-7040-5204

Rajiv Nadukuru (R)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Alana C Jones (AC)

Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
ORCID: 0000-0003-3827-2426

Edyta Malolepsza (E)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Ozan Dikilitas (O)

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
ORCID: 0000-0002-9906-8608

Iftikhar J Kullo (IJ)

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
ORCID: 0000-0002-6524-3471

Daniel J Schaid (DJ)

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.

Elizabeth Karlson (E)

Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Tian Ge (T)

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.

James B Meigs (JB)

Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.

Jordan W Smoller (JW)

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.

Christoph Lange (C)

Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

David R Crosslin (DR)

Division of Biomedical Informatics and Genomics, John W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.

Gail P Jarvik (GP)

Departments of Medicine (Medical Genetics) and Genome Sciences, University of Washington, Seattle, WA, USA.

Pavan K Bhatraju (PK)

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.

Jacklyn N Hellwege (JN)

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
ORCID: 0000-0001-7479-0920

Paulette Chandler (P)

Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Laura Rasmussen Torvik (LR)

Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Alex Fedotov (A)

Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA.

Cong Liu (C)

Department of Biomedical Informatics, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.

Christopher Kachulis (C)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Niall Lennon (N)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Noura S Abul-Husn (NS)

Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0002-5179-1944

Judy H Cho (JH)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0002-7959-0466

Iuliana Ionita-Laza (I)

Department of Biostatistics, Columbia University, New York, NY, USA.

Ali G Gharavi (AG)

Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
ORCID: 0000-0003-2801-233X

Wendy K Chung (WK)

Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.

George Hripcsak (G)

Department of Biomedical Informatics, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.

Chunhua Weng (C)

Department of Biomedical Informatics, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
ORCID: 0000-0002-9624-0214

Girish Nadkarni (G)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0001-6319-4314

Marguerite R Irvin (MR)

Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.

Hemant K Tiwari (HK)

Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.

Eimear E Kenny (EE)

Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Nita A Limdi (NA)

Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Krzysztof Kiryluk (K)

Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA. kk473@columbia.edu.
ORCID: 0000-0002-5047-6715

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Lipoprotéines › Apolipoprotéines › Apolipoprotéines L › Apolipoprotéine L1 › Genome-wide polygenic score to predict chronic...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Genome-wide polygenic score to predict chronic...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genome-wide polygenic score to predict chronic...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Genome-wide polygenic score to predict chronic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genome-wide polygenic score to predict chronic...
questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Hérédité multifactorielle › Genome-wide polygenic score to predict chronic...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Genome-wide polygenic score to predict chronic...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Insuffisance rénale chronique › Genome-wide polygenic score to predict chronic...