Genome-wide association analysis of cystatin-C kidney function in continental Africa.

Humans Bayes Theorem Creatinine Cystatin C / genetics Genome-Wide Association Study Kidney / physiology Uganda
Continental Africa Cystatin-C Estimated glomerular filtration rate Fine-mapping Genome-wide association study Kidney function

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Sep 2023
Historique:
received: 05 06 2023
revised: 08 08 2023
accepted: 11 08 2023
medline: 18 9 2023
pubmed: 29 8 2023
entrez: 28 8 2023
Statut: ppublish

Résumé

Chronic kidney disease is becoming more prevalent in Africa, and its genetic determinants are poorly understood. Creatinine-based estimated glomerular filtration rate (eGFR) is commonly used to estimate kidney function, modelling the excretion of the endogenous biomarker (creatinine). However, eGFR based on creatinine has been shown to inadequately detect individuals with low kidney function in Sub-Saharan Africa, with eGFR based on cystatin-C (eGFRcys) exhibiting significantly superior performance. Therefore, we opted to conduct a GWAS for eGFRcys. Using the Uganda Genomic Resource, we performed a genome-wide association study (GWAS) of eGFRcys in 5877 Ugandans and evaluated replication in independent studies. Subsequently, putative causal variants were screened through Bayesian fine-mapping. Functional annotation of the GWAS loci was performed using Functional Mapping and Annotation (FUMA). Three independent lead single nucleotide polymorphisms (SNPs) (P-value <5 × 10 Our study found two previously unreported associated SNPs for eGFRcys in continental Africans (rs59288815 and rs4277141) and validated a previously well-established SNP (rs911119) for eGFRcys. The identified gene-set enrichment for the G-protein signalling pathways relates to the capacity of the kidney to readily adapt to an ever-changing environment. Additional GWASs are required to represent the diverse regions in Africa. Wellcome (220740/Z/20/Z).

Sections du résumé

BACKGROUND BACKGROUND
Chronic kidney disease is becoming more prevalent in Africa, and its genetic determinants are poorly understood. Creatinine-based estimated glomerular filtration rate (eGFR) is commonly used to estimate kidney function, modelling the excretion of the endogenous biomarker (creatinine). However, eGFR based on creatinine has been shown to inadequately detect individuals with low kidney function in Sub-Saharan Africa, with eGFR based on cystatin-C (eGFRcys) exhibiting significantly superior performance. Therefore, we opted to conduct a GWAS for eGFRcys.
METHODS METHODS
Using the Uganda Genomic Resource, we performed a genome-wide association study (GWAS) of eGFRcys in 5877 Ugandans and evaluated replication in independent studies. Subsequently, putative causal variants were screened through Bayesian fine-mapping. Functional annotation of the GWAS loci was performed using Functional Mapping and Annotation (FUMA).
FINDINGS RESULTS
Three independent lead single nucleotide polymorphisms (SNPs) (P-value <5 × 10
INTERPRETATION CONCLUSIONS
Our study found two previously unreported associated SNPs for eGFRcys in continental Africans (rs59288815 and rs4277141) and validated a previously well-established SNP (rs911119) for eGFRcys. The identified gene-set enrichment for the G-protein signalling pathways relates to the capacity of the kidney to readily adapt to an ever-changing environment. Additional GWASs are required to represent the diverse regions in Africa.
FUNDING BACKGROUND
Wellcome (220740/Z/20/Z).

Identifiants

DOI: 10.1016/j.ebiom.2023.104775 PMID: 37639939 PMC: PMC10474146
pubmed: 37639939
pii: S2352-3964(23)00341-9
doi: 10.1016/j.ebiom.2023.104775
pmc: PMC10474146
pii:
doi:

Substances chimiques

Creatinine AYI8EX34EU
Cystatin C 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

104775

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00033/3
Pays : United Kingdom

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests None declared.

Auteurs

Richard Mayanja (R)

The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda; Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University, College of Health Sciences, Kampala, Uganda.

Tafadzwa Machipisa (T)

Department of Medicine, University of Cape Town & Groote Schuur Hospital, Cape Town, South Africa; Clinical Research Laboratory-Genetic and Molecular Epidemiology Laboratory (CRLB-GMEL), Population Health Research Institute (PHRI) & McMaster University, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, Ontario, L8L 2X2, Canada.

Opeyemi Soremekun (O)

The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda.

Abram B Kamiza (AB)

The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda; Malawi Epidemiology and Intervention Research Unit, Lilongwe, Malawi.

Christopher Kintu (C)

The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda; Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University, College of Health Sciences, Kampala, Uganda.

Allan Kalungi (A)

The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda.

Robert Kalyesubula (R)

Medical Research Council/ Uganda Virus Research Institute (MRC/UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe, Uganda.

Obondo J Sande (OJ)

Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University, College of Health Sciences, Kampala, Uganda.

Daudi Jjingo (D)

African Center of Excellence in Bioinformatics (ACE-B), Makerere University, Kampala, Uganda.

June Fabian (J)

Medical Research Council/Wits University Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Wits Donald Gordon Medical Centre, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Cassianne Robinson-Cohen (C)

Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Nora Franceschini (N)

Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.

Dorothea Nitsch (D)

London School of Hygiene and Tropical Medicine London, UK.

Moffat Nyirenda (M)

Clinical Research Laboratory-Genetic and Molecular Epidemiology Laboratory (CRLB-GMEL), Population Health Research Institute (PHRI) & McMaster University, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, Ontario, L8L 2X2, Canada; London School of Hygiene and Tropical Medicine London, UK.

Eleftheria Zeggini (E)

Institute of Translational Genomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; TUM School of Medicine, Translational Genomics, Technical University of Munich and Klinikum Rechts der Isar, Munich, Germany.

Andrew P Morris (AP)

Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, UK.

Tinashe Chikowore (T)

Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; MRC/Wits Developmental Pathways for Health Research Unit, Department of Pediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Segun Fatumo (S)

The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda; Medical Research Council/ Uganda Virus Research Institute (MRC/UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe, Uganda; London School of Hygiene and Tropical Medicine London, UK; Institute of Translational Genomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. Electronic address: segun.fatumo@lshtm.ac.uk.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genome-wide association analysis of cystatin-C...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Théorème de Bayes › Genome-wide association analysis of cystatin-C...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Imidazoles › Créatinine › Genome-wide association analysis of cystatin-C...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Cystatines › Cystatine C › Genome-wide association analysis of cystatin-C...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genome-wide association analysis of cystatin-C...
questionsmedicales.fr › Appareil urogénital › Voies urinaires › Rein › Genome-wide association analysis of cystatin-C...
questionsmedicales.fr › Régions géographiques › Afrique › Afrique subsaharienne › Afrique de l'Est › Ouganda › Genome-wide association analysis of cystatin-C...