Skip to main content

Genetic association for renal traits among participants of African ancestry reveals new loci for renal function.

Publication ,  Journal Article
Liu, C-T; Garnaas, MK; Tin, A; Kottgen, A; Franceschini, N; Peralta, CA; de Boer, IH; Lu, X; Atkinson, E; Ding, J; Nalls, M; Shriner, D ...
Published in: PLoS Genet
September 2011

Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m(2)), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10(-7)) and FNDC1 (p-value = 3.0×10(-7)) for UACR, and KCNQ1 with eGFR (p = 3.6×10(-6)). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

September 2011

Volume

7

Issue

9

Start / End Page

e1002264

Location

United States

Related Subject Headings

  • Zebrafish
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Neoplasm Proteins
  • Middle Aged
  • Male
  • Kidney Failure, Chronic
  • Kidney
  • KCNQ1 Potassium Channel
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, C.-T., Garnaas, M. K., Tin, A., Kottgen, A., Franceschini, N., Peralta, C. A., … Fox, C. S. (2011). Genetic association for renal traits among participants of African ancestry reveals new loci for renal function. PLoS Genet, 7(9), e1002264. https://doi.org/10.1371/journal.pgen.1002264
Liu, Ching-Ti, Maija K. Garnaas, Adrienne Tin, Anna Kottgen, Nora Franceschini, Carmen A. Peralta, Ian H. de Boer, et al. “Genetic association for renal traits among participants of African ancestry reveals new loci for renal function.PLoS Genet 7, no. 9 (September 2011): e1002264. https://doi.org/10.1371/journal.pgen.1002264.
Liu C-T, Garnaas MK, Tin A, Kottgen A, Franceschini N, Peralta CA, et al. Genetic association for renal traits among participants of African ancestry reveals new loci for renal function. PLoS Genet. 2011 Sep;7(9):e1002264.
Liu, Ching-Ti, et al. “Genetic association for renal traits among participants of African ancestry reveals new loci for renal function.PLoS Genet, vol. 7, no. 9, Sept. 2011, p. e1002264. Pubmed, doi:10.1371/journal.pgen.1002264.
Liu C-T, Garnaas MK, Tin A, Kottgen A, Franceschini N, Peralta CA, de Boer IH, Lu X, Atkinson E, Ding J, Nalls M, Shriner D, Coresh J, Kutlar A, Bibbins-Domingo K, Siscovick D, Akylbekova E, Wyatt S, Astor B, Mychaleckjy J, Li M, Reilly MP, Townsend RR, Adeyemo A, Zonderman AB, de Andrade M, Turner ST, Mosley TH, Harris TB, CKDGen Consortium, Rotimi CN, Liu Y, Kardia SLR, Evans MK, Shlipak MG, Kramer H, Flessner MF, Dreisbach AW, Goessling W, Cupples LA, Kao WL, Fox CS. Genetic association for renal traits among participants of African ancestry reveals new loci for renal function. PLoS Genet. 2011 Sep;7(9):e1002264.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

September 2011

Volume

7

Issue

9

Start / End Page

e1002264

Location

United States

Related Subject Headings

  • Zebrafish
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Neoplasm Proteins
  • Middle Aged
  • Male
  • Kidney Failure, Chronic
  • Kidney
  • KCNQ1 Potassium Channel
  • Humans