title: Effect of Genetic African Ancestry on eGFR and Kidney Disease.
abstract: Self-reported ancestry, genetically determined ancestry, and APOL1 polymorphisms are associated with variation in kidney function and related disease risk, but the relative importance of these factors remains unclear. We estimated the global proportion of African ancestry for 9048 individuals at Mount Sinai Medical Center in Manhattan (3189 African Americans, 1721 European Americans, and 4138 Hispanic/Latino Americans by self-report) using genome-wide genotype data. CKD-EPI eGFR and genotypes of three APOL1 coding variants were available. In admixed African Americans and Hispanic/Latino Americans, serum creatinine values increased as African ancestry increased (per 10% increase in African ancestry, creatinine values increased 1% in African Americans and 0.9% in Hispanic/Latino Americans; P≤1x10(-7)). eGFR was likewise significantly associated with African genetic ancestry in both populations. In contrast, APOL1 risk haplotypes were significantly associated with CKD, eGFR<45 ml/min per 1.73 m(2), and ESRD, with effects increasing with worsening disease states and the contribution of genetic African ancestry decreasing in parallel. Using genetic ancestry in the eGFR equation to reclassify patients as black on the basis of ≥50% African ancestry resulted in higher eGFR for 14.7% of Hispanic/Latino Americans and lower eGFR for 4.1% of African Americans, affecting CKD staging in 4.3% and 1% of participants, respectively. Reclassified individuals had electrolyte values consistent with their newly assigned CKD stage. In summary, proportion of African ancestry was significantly associated with normal-range creatinine and eGFR, whereas APOL1 risk haplotypes drove the associations with CKD. Recalculation of eGFR on the basis of genetic ancestry affected CKD staging and warrants additional investigation.
authors.affiliation: Departments of Medicine and Genetics and Genomic Sciences, The Charles Bronfman Institute for Personalized Medicine, mudler@mgh.harvard.edu.
authors.forename: Miriam S
authors.initials: MS
authors.lastname: Udler
authors.affiliation: Departments of Medicine and The Charles Bronfman Institute for Personalized Medicine, Division of Nephrology.
authors.forename: Girish N
authors.initials: GN
authors.lastname: Nadkarni
authors.affiliation: Genetics and Genomic Sciences, The Charles Bronfman Institute for Personalized Medicine.
authors.forename: Gillian
authors.initials: G
authors.lastname: Belbin
authors.affiliation: The Charles Bronfman Institute for Personalized Medicine.
authors.forename: Vaneet
authors.initials: V
authors.lastname: Lotay
authors.affiliation: Departments of Medicine and Division of Nephrology.
authors.forename: Christina
authors.initials: C
authors.lastname: Wyatt
authors.affiliation: Departments of Medicine and The Charles Bronfman Institute for Personalized Medicine.
authors.forename: Omri
authors.initials: O
authors.lastname: Gottesman
authors.affiliation: Departments of Medicine and The Charles Bronfman Institute for Personalized Medicine, Division of Nephrology.
authors.forename: Erwin P
authors.initials: EP
authors.lastname: Bottinger
authors.affiliation: Genetics and Genomic Sciences, The Charles Bronfman Institute for Personalized Medicine, The Center for Statistical Genetics, and The Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Eimear E
authors.initials: EE
authors.lastname: Kenny
authors.affiliation: Genetics and Genomic Sciences, The Charles Bronfman Institute for Personalized Medicine, The Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Inga
authors.initials: I
authors.lastname: Peter
mesh_terms: D001741:Black or African American / Q000235:genetics; D017677:Age Distribution; D000368:Aged; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D044383:Black People / Q000235:genetics; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005919:Glomerular Filtration Rate / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D015994:Incidence; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D051436:Renal Insufficiency, Chronic / Q000208:ethnology* / Q000235:genetics*; D017678:Sex Distribution; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: GFR; apolipoprotein L1; epidemiology and outcomes; ethnicity; genetic renal disease; renal function