APOL1 Bi-and Monoallelic Variants and Chronic Kidney Disease in West Africans.

Rasheed A. Gbadegesin; Ifeoma Ulasi; Samuel Ajayi; Yemi Raji; Timothy Olanrewaju; Charlotte Osafo; Adebowale D. Ademola; Adanze Asinobi; Cheryl A. Winkler; David Burke; Fatiu Arogundade; Ivy Ekem; Jacob Plange-Rhule; Manmak Mamven; Michael Matekole; Olukemi Amodu; Richard Cooper; Sampson Antwi; Adebowale A. Adeyemo; Titilayo O. Ilori; Victoria Adabayeri; Alexander Nyarko; Anita Ghansah; Toyin Amira; Adaobi Solarin; Olugbenga Awobusuyi; Paul L. Kimmel; Frank Chip Brosius; Muhammad Makusidi; Uzoma Odenigbo; Matthias Kretzler; Jeffrey B. Hodgin; Martin R. Pollak; Vincent Boima; Barry I. Freedman; Nicholette D. Palmer; Bernard Collins; Milind Phadnis; Jill Smith; Celia I. Agwai; Ogochukwu Okoye; Aliyu Abdu; Jillian Wilson; Winfred Williams; Babatunde L. Salako; Rulan S. Parekh; Bamidele Tayo; Dwomoa Adu; Akinlolu Ojo

doi:10.1056/NEJMoa2404211

APOL1 Bi-and Monoallelic Variants and Chronic Kidney Disease in West Africans.

Rasheed A. Gbadegesin
, Ifeoma Ulasi
, Samuel Ajayi
, Yemi Raji
, Timothy Olanrewaju
, Charlotte Osafo
, Adebowale D. Ademola
, Adanze Asinobi
, Cheryl A. Winkler
, David Burke
, Fatiu Arogundade
, Ivy Ekem
, Jacob Plange-Rhule
, Manmak Mamven
, Michael Matekole
, Olukemi Amodu
, Richard Cooper
, Sampson Antwi
, Adebowale A. Adeyemo
, Titilayo O. Ilori

Victoria Adabayeri, Alexander Nyarko, Anita Ghansah, Toyin Amira, Adaobi Solarin, Olugbenga Awobusuyi, Paul L. Kimmel, Frank Chip Brosius, Muhammad Makusidi, Uzoma Odenigbo, Matthias Kretzler, Jeffrey B. Hodgin, Martin R. Pollak, Vincent Boima, Barry I. Freedman, Nicholette D. Palmer, Bernard Collins, Milind Phadnis, Jill Smith, Celia I. Agwai, Ogochukwu Okoye, Aliyu Abdu, Jillian Wilson, Winfred Williams, Babatunde L. Salako, Rulan S. Parekh, Bamidele Tayo, Dwomoa Adu, Akinlolu Ojo

Duke University Medical Center
University of Nigeria
College of Medicine, University of Ibadan
University of Ilorin
University of Ghana
National Cancer Institute at Frederick
University of Michigan Medical School
Obafemi Awolowo University
University of Cape Coast Ghana
Kwame Nkrumah University of Science and Technology
University of Abuja
Loyola University Chicago
National Human Genome Research Institute (NHGRI)
Boston University Chobanian & Avedisian School of Medicine
College of Medicine, University of Lagos
Lagos State University
National Institutes of Health
University of Arizona
Usmanu Danfodiyo University
Nnamdi Azikiwe University
Massachusetts General Hospital
Wake Forest University
University of Kansas Medical Center
Aminu Kano Teaching Hospital
University of Toronto

Research output: Contribution to journal › Article › peer-review

58 Citations (Scopus)

Abstract

Background Apolipoprotein L1 gene (APOL1) variants are risk factors for chronic kidney disease (CKD) among Black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of APOL1 variants with CKD in West Africans, a major group in the Black population. Methods We conducted a case-control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease. We analyzed the association of CKD with APOL1 variants among participants with high-risk genotypes (two APOL1 risk alleles) and those with low-risk genotypes (fewer than two APOL1 risk alleles) by fitting logistic-regression models that controlled for covariates, including clinical site, age, and sex. Results Among 8355 participants (4712 with CKD stages 2 through 5, 866 with glomerular diseases, and 2777 with no kidney disease), the prevalence of monoallelic APOL1 variants was 43.0% and that of biallelic APOL1 variants was 29.7%. Participants with two APOL1 risk alleles had higher odds of having CKD than those with one risk allele or no risk alleles (adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.11 to 1.40), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.84; 95% CI, 1.30 to 2.61). Participants with one APOL1 risk allele had higher odds of having CKD than those with no risk alleles (adjusted odds ratio, 1.18; 95% CI, 1.04 to 1.33), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.61; 95% CI, 1.04 to 2.48). The inclusion of covariates did not modify the association of monoallelic and biallelic APOL1 variants with CKD or focal segmental glomerulosclerosis. Conclusions In this study, monoallelic APOL1 variants were associated with 18% higher odds of CKD and 61% higher odds of focal segmental glomerulosclerosis; biallelic APOL1 variants were associated with 25% higher odds of CKD and 84% higher odds of focal segmental glomerulosclerosis. (Funded by the National Human Genome Research Institute and others.)

Original language	English
Pages (from-to)	228-238
Number of pages	11
Journal	New England Journal of Medicine
Volume	392
Issue number	3
DOIs	https://doi.org/10.1056/NEJMoa2404211
Publication status	Published - 16 Jan 2025
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Chronic Kidney Disease
Clinical Medicine
Clinical Medicine General
Diversity, Equity, and Inclusion
Genetics
Genetics General
Glomerular Disease
Nephrology
Race/Ethnicity

Access to Document

10.1056/NEJMoa2404211

Cite this

Gbadegesin, R. A., Ulasi, I., Ajayi, S., Raji, Y., Olanrewaju, T., Osafo, C., Ademola, A. D., Asinobi, A., Winkler, C. A., Burke, D., Arogundade, F., Ekem, I., Plange-Rhule, J., Mamven, M., Matekole, M., Amodu, O., Cooper, R., Antwi, S., Adeyemo, A. A., ... Ojo, A. (2025). APOL1 Bi-and Monoallelic Variants and Chronic Kidney Disease in West Africans. New England Journal of Medicine, 392(3), 228-238. https://doi.org/10.1056/NEJMoa2404211

@article{3ac1f250f5da444c80f21568b4e1c40b,

title = "APOL1 Bi-and Monoallelic Variants and Chronic Kidney Disease in West Africans.",

abstract = "Background Apolipoprotein L1 gene (APOL1) variants are risk factors for chronic kidney disease (CKD) among Black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of APOL1 variants with CKD in West Africans, a major group in the Black population. Methods We conducted a case-control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease. We analyzed the association of CKD with APOL1 variants among participants with high-risk genotypes (two APOL1 risk alleles) and those with low-risk genotypes (fewer than two APOL1 risk alleles) by fitting logistic-regression models that controlled for covariates, including clinical site, age, and sex. Results Among 8355 participants (4712 with CKD stages 2 through 5, 866 with glomerular diseases, and 2777 with no kidney disease), the prevalence of monoallelic APOL1 variants was 43.0\% and that of biallelic APOL1 variants was 29.7\%. Participants with two APOL1 risk alleles had higher odds of having CKD than those with one risk allele or no risk alleles (adjusted odds ratio, 1.25; 95\% confidence interval [CI], 1.11 to 1.40), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.84; 95\% CI, 1.30 to 2.61). Participants with one APOL1 risk allele had higher odds of having CKD than those with no risk alleles (adjusted odds ratio, 1.18; 95\% CI, 1.04 to 1.33), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.61; 95\% CI, 1.04 to 2.48). The inclusion of covariates did not modify the association of monoallelic and biallelic APOL1 variants with CKD or focal segmental glomerulosclerosis. Conclusions In this study, monoallelic APOL1 variants were associated with 18\% higher odds of CKD and 61\% higher odds of focal segmental glomerulosclerosis; biallelic APOL1 variants were associated with 25\% higher odds of CKD and 84\% higher odds of focal segmental glomerulosclerosis. (Funded by the National Human Genome Research Institute and others.)",

keywords = "Chronic Kidney Disease, Clinical Medicine, Clinical Medicine General, Diversity, Equity, and Inclusion, Genetics, Genetics General, Glomerular Disease, Nephrology, Race/Ethnicity",

author = "Gbadegesin, \{Rasheed A.\} and Ifeoma Ulasi and Samuel Ajayi and Yemi Raji and Timothy Olanrewaju and Charlotte Osafo and Ademola, \{Adebowale D.\} and Adanze Asinobi and Winkler, \{Cheryl A.\} and David Burke and Fatiu Arogundade and Ivy Ekem and Jacob Plange-Rhule and Manmak Mamven and Michael Matekole and Olukemi Amodu and Richard Cooper and Sampson Antwi and Adeyemo, \{Adebowale A.\} and Ilori, \{Titilayo O.\} and Victoria Adabayeri and Alexander Nyarko and Anita Ghansah and Toyin Amira and Adaobi Solarin and Olugbenga Awobusuyi and Kimmel, \{Paul L.\} and Brosius, \{Frank Chip\} and Muhammad Makusidi and Uzoma Odenigbo and Matthias Kretzler and Hodgin, \{Jeffrey B.\} and Pollak, \{Martin R.\} and Vincent Boima and Freedman, \{Barry I.\} and Palmer, \{Nicholette D.\} and Bernard Collins and Milind Phadnis and Jill Smith and Agwai, \{Celia I.\} and Ogochukwu Okoye and Aliyu Abdu and Jillian Wilson and Winfred Williams and Salako, \{Babatunde L.\} and Parekh, \{Rulan S.\} and Bamidele Tayo and Dwomoa Adu and Akinlolu Ojo",

note = "Publisher Copyright: {\textcopyright} 2024 Massachusetts Medical Society.",

year = "2025",

month = jan,

day = "16",

doi = "10.1056/NEJMoa2404211",

language = "English",

volume = "392",

pages = "228--238",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "3",

}

Gbadegesin, RA, Ulasi, I, Ajayi, S, Raji, Y, Olanrewaju, T, Osafo, C, Ademola, AD, Asinobi, A, Winkler, CA, Burke, D, Arogundade, F, Ekem, I, Plange-Rhule, J, Mamven, M, Matekole, M, Amodu, O, Cooper, R, Antwi, S, Adeyemo, AA, Ilori, TO, Adabayeri, V, Nyarko, A, Ghansah, A, Amira, T, Solarin, A, Awobusuyi, O, Kimmel, PL, Brosius, FC, Makusidi, M, Odenigbo, U, Kretzler, M, Hodgin, JB, Pollak, MR, Boima, V, Freedman, BI, Palmer, ND, Collins, B, Phadnis, M, Smith, J, Agwai, CI, Okoye, O, Abdu, A, Wilson, J, Williams, W, Salako, BL, Parekh, RS, Tayo, B, Adu, D & Ojo, A 2025, 'APOL1 Bi-and Monoallelic Variants and Chronic Kidney Disease in West Africans.', New England Journal of Medicine, vol. 392, no. 3, pp. 228-238. https://doi.org/10.1056/NEJMoa2404211

TY - JOUR

T1 - APOL1 Bi-and Monoallelic Variants and Chronic Kidney Disease in West Africans.

AU - Gbadegesin, Rasheed A.

AU - Ulasi, Ifeoma

AU - Ajayi, Samuel

AU - Raji, Yemi

AU - Olanrewaju, Timothy

AU - Osafo, Charlotte

AU - Ademola, Adebowale D.

AU - Asinobi, Adanze

AU - Winkler, Cheryl A.

AU - Burke, David

AU - Arogundade, Fatiu

AU - Ekem, Ivy

AU - Plange-Rhule, Jacob

AU - Mamven, Manmak

AU - Matekole, Michael

AU - Amodu, Olukemi

AU - Cooper, Richard

AU - Antwi, Sampson

AU - Adeyemo, Adebowale A.

AU - Ilori, Titilayo O.

AU - Adabayeri, Victoria

AU - Nyarko, Alexander

AU - Ghansah, Anita

AU - Amira, Toyin

AU - Solarin, Adaobi

AU - Awobusuyi, Olugbenga

AU - Kimmel, Paul L.

AU - Brosius, Frank Chip

AU - Makusidi, Muhammad

AU - Odenigbo, Uzoma

AU - Kretzler, Matthias

AU - Hodgin, Jeffrey B.

AU - Pollak, Martin R.

AU - Boima, Vincent

AU - Freedman, Barry I.

AU - Palmer, Nicholette D.

AU - Collins, Bernard

AU - Phadnis, Milind

AU - Smith, Jill

AU - Agwai, Celia I.

AU - Okoye, Ogochukwu

AU - Abdu, Aliyu

AU - Wilson, Jillian

AU - Williams, Winfred

AU - Salako, Babatunde L.

AU - Parekh, Rulan S.

AU - Tayo, Bamidele

AU - Adu, Dwomoa

AU - Ojo, Akinlolu

PY - 2025/1/16

Y1 - 2025/1/16

N2 - Background Apolipoprotein L1 gene (APOL1) variants are risk factors for chronic kidney disease (CKD) among Black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of APOL1 variants with CKD in West Africans, a major group in the Black population. Methods We conducted a case-control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease. We analyzed the association of CKD with APOL1 variants among participants with high-risk genotypes (two APOL1 risk alleles) and those with low-risk genotypes (fewer than two APOL1 risk alleles) by fitting logistic-regression models that controlled for covariates, including clinical site, age, and sex. Results Among 8355 participants (4712 with CKD stages 2 through 5, 866 with glomerular diseases, and 2777 with no kidney disease), the prevalence of monoallelic APOL1 variants was 43.0% and that of biallelic APOL1 variants was 29.7%. Participants with two APOL1 risk alleles had higher odds of having CKD than those with one risk allele or no risk alleles (adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.11 to 1.40), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.84; 95% CI, 1.30 to 2.61). Participants with one APOL1 risk allele had higher odds of having CKD than those with no risk alleles (adjusted odds ratio, 1.18; 95% CI, 1.04 to 1.33), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.61; 95% CI, 1.04 to 2.48). The inclusion of covariates did not modify the association of monoallelic and biallelic APOL1 variants with CKD or focal segmental glomerulosclerosis. Conclusions In this study, monoallelic APOL1 variants were associated with 18% higher odds of CKD and 61% higher odds of focal segmental glomerulosclerosis; biallelic APOL1 variants were associated with 25% higher odds of CKD and 84% higher odds of focal segmental glomerulosclerosis. (Funded by the National Human Genome Research Institute and others.)

AB - Background Apolipoprotein L1 gene (APOL1) variants are risk factors for chronic kidney disease (CKD) among Black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of APOL1 variants with CKD in West Africans, a major group in the Black population. Methods We conducted a case-control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease. We analyzed the association of CKD with APOL1 variants among participants with high-risk genotypes (two APOL1 risk alleles) and those with low-risk genotypes (fewer than two APOL1 risk alleles) by fitting logistic-regression models that controlled for covariates, including clinical site, age, and sex. Results Among 8355 participants (4712 with CKD stages 2 through 5, 866 with glomerular diseases, and 2777 with no kidney disease), the prevalence of monoallelic APOL1 variants was 43.0% and that of biallelic APOL1 variants was 29.7%. Participants with two APOL1 risk alleles had higher odds of having CKD than those with one risk allele or no risk alleles (adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.11 to 1.40), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.84; 95% CI, 1.30 to 2.61). Participants with one APOL1 risk allele had higher odds of having CKD than those with no risk alleles (adjusted odds ratio, 1.18; 95% CI, 1.04 to 1.33), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.61; 95% CI, 1.04 to 2.48). The inclusion of covariates did not modify the association of monoallelic and biallelic APOL1 variants with CKD or focal segmental glomerulosclerosis. Conclusions In this study, monoallelic APOL1 variants were associated with 18% higher odds of CKD and 61% higher odds of focal segmental glomerulosclerosis; biallelic APOL1 variants were associated with 25% higher odds of CKD and 84% higher odds of focal segmental glomerulosclerosis. (Funded by the National Human Genome Research Institute and others.)

KW - Chronic Kidney Disease

KW - Clinical Medicine

KW - Clinical Medicine General

KW - Diversity, Equity, and Inclusion

KW - Genetics

KW - Genetics General

KW - Glomerular Disease

KW - Nephrology

KW - Race/Ethnicity

UR - https://www.scopus.com/pages/publications/85216036665

U2 - 10.1056/NEJMoa2404211

DO - 10.1056/NEJMoa2404211

M3 - Article

C2 - 39465900

AN - SCOPUS:85216036665

SN - 0028-4793

VL - 392

SP - 228

EP - 238

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 3

ER -

APOL1 Bi-and Monoallelic Variants and Chronic Kidney Disease in West Africans.

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