title: Multiple loci associated with renal function in African Americans.
abstract: 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.
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, Maryland, USA. shrinerda@mail.nih.gov
authors.forename: Daniel
authors.initials: D
authors.lastname: Shriner
authors.forename: Alan
authors.initials: A
authors.lastname: Herbert
authors.forename: Ayo P
authors.initials: AP
authors.lastname: Doumatey
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Hanxia
authors.initials: H
authors.lastname: Huang
authors.forename: Michael R
authors.initials: MR
authors.lastname: Erdos
authors.forename: Guanjie
authors.initials: G
authors.lastname: Chen
authors.forename: Norman P
authors.initials: NP
authors.lastname: Gerry
authors.forename: Michael F
authors.initials: MF
authors.lastname: Christman
authors.forename: Adebowale
authors.initials: A
authors.lastname: Adeyemo
authors.forename: Charles N
authors.initials: CN
authors.lastname: Rotimi
mesh_terms: D001741:Black or African American / Q000235:genetics*; D005260:Female; D005789:Genealogy and Heraldry; D056426:Genetic Loci / Q000235:genetics*; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics