Multiple loci associated with renal function in African Americans.

The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals...

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Main Authors: Daniel Shriner, Alan Herbert, Ayo P Doumatey, Jie Zhou, Hanxia Huang, Michael R Erdos, Guanjie Chen, Norman P Gerry, Michael F Christman, Adebowale Adeyemo, Charles N Rotimi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0045112&type=printable
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author Daniel Shriner
Alan Herbert
Ayo P Doumatey
Jie Zhou
Hanxia Huang
Michael R Erdos
Guanjie Chen
Norman P Gerry
Michael F Christman
Adebowale Adeyemo
Charles N Rotimi
author_facet Daniel Shriner
Alan Herbert
Ayo P Doumatey
Jie Zhou
Hanxia Huang
Michael R Erdos
Guanjie Chen
Norman P Gerry
Michael F Christman
Adebowale Adeyemo
Charles N Rotimi
author_sort Daniel Shriner
collection DOAJ
description The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR). We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.
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spelling doaj-art-07b26f80e4bb426484403ccaf2eca74e2025-08-20T03:26:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4511210.1371/journal.pone.0045112Multiple loci associated with renal function in African Americans.Daniel ShrinerAlan HerbertAyo P DoumateyJie ZhouHanxia HuangMichael R ErdosGuanjie ChenNorman P GerryMichael F ChristmanAdebowale AdeyemoCharles N RotimiThe incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR). We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0045112&type=printable
spellingShingle Daniel Shriner
Alan Herbert
Ayo P Doumatey
Jie Zhou
Hanxia Huang
Michael R Erdos
Guanjie Chen
Norman P Gerry
Michael F Christman
Adebowale Adeyemo
Charles N Rotimi
Multiple loci associated with renal function in African Americans.
PLoS ONE
title Multiple loci associated with renal function in African Americans.
title_full Multiple loci associated with renal function in African Americans.
title_fullStr Multiple loci associated with renal function in African Americans.
title_full_unstemmed Multiple loci associated with renal function in African Americans.
title_short Multiple loci associated with renal function in African Americans.
title_sort multiple loci associated with renal function in african americans
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0045112&type=printable
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