Skip to main content

SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function.

Publication ,  Journal Article
Li, M; Li, Y; Weeks, O; Mijatovic, V; Teumer, A; Huffman, JE; Tromp, G; Fuchsberger, C; Gorski, M; Lyytikäinen, L-P; Nutile, T; Sedaghat, S ...
Published in: J Am Soc Nephrol
March 2017

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1<3.7×10-7), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4×10-8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

March 2017

Volume

28

Issue

3

Start / End Page

981 / 994

Location

United States

Related Subject Headings

  • Zebrafish
  • Urology & Nephrology
  • Son of Sevenless Proteins
  • Proto-Oncogene Proteins
  • Protein Tyrosine Phosphatases
  • Kidney
  • Humans
  • Glomerular Filtration Rate
  • Genome-Wide Association Study
  • Genetic Loci
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Li, M., Li, Y., Weeks, O., Mijatovic, V., Teumer, A., Huffman, J. E., … Chu, A. Y. (2017). SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function. J Am Soc Nephrol, 28(3), 981–994. https://doi.org/10.1681/ASN.2016020131
Li, Man, Yong Li, Olivia Weeks, Vladan Mijatovic, Alexander Teumer, Jennifer E. Huffman, Gerard Tromp, et al. “SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function.J Am Soc Nephrol 28, no. 3 (March 2017): 981–94. https://doi.org/10.1681/ASN.2016020131.
Li M, Li Y, Weeks O, Mijatovic V, Teumer A, Huffman JE, et al. SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function. J Am Soc Nephrol. 2017 Mar;28(3):981–94.
Li, Man, et al. “SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function.J Am Soc Nephrol, vol. 28, no. 3, Mar. 2017, pp. 981–94. Pubmed, doi:10.1681/ASN.2016020131.
Li M, Li Y, Weeks O, Mijatovic V, Teumer A, Huffman JE, Tromp G, Fuchsberger C, Gorski M, Lyytikäinen L-P, Nutile T, Sedaghat S, Sorice R, Tin A, Yang Q, Ahluwalia TS, Arking DE, Bihlmeyer NA, Böger CA, Carroll RJ, Chasman DI, Cornelis MC, Dehghan A, Faul JD, Feitosa MF, Gambaro G, Gasparini P, Giulianini F, Heid I, Huang J, Imboden M, Jackson AU, Jeff J, Jhun MA, Katz R, Kifley A, Kilpeläinen TO, Kumar A, Laakso M, Li-Gao R, Lohman K, Lu Y, Mägi R, Malerba G, Mihailov E, Mohlke KL, Mook-Kanamori DO, Robino A, Ruderfer D, Salvi E, Schick UM, Schulz C-A, Smith AV, Smith JA, Traglia M, Yerges-Armstrong LM, Zhao W, Goodarzi MO, Kraja AT, Liu C, Wessel J, CHARGE Glycemic-T2D Working Group, CHARGE Blood Pressure Working Group, Boerwinkle E, Borecki IB, Bork-Jensen J, Bottinger EP, Braga D, Brandslund I, Brody JA, Campbell A, Carey DJ, Christensen C, Coresh J, Crook E, Curhan GC, Cusi D, de Boer IH, de Vries APJ, Denny JC, Devuyst O, Dreisbach AW, Endlich K, Esko T, Franco OH, Fulop T, Gerhard GS, Glümer C, Gottesman O, Grarup N, Gudnason V, Hansen T, Harris TB, Hayward C, Hocking L, Hofman A, Hu FB, Husemoen LLN, Jackson RD, Jørgensen T, Jørgensen ME, Kähönen M, Kardia SLR, König W, Kooperberg C, Kriebel J, Launer LJ, Lauritzen T, Lehtimäki T, Levy D, Linksted P, Linneberg A, Liu Y, Loos RJF, Lupo A, Meisinger C, Melander O, Metspalu A, Mitchell P, Nauck M, Nürnberg P, Orho-Melander M, Parsa A, Pedersen O, Peters A, Peters U, Polasek O, Porteous D, Probst-Hensch NM, Psaty BM, Qi L, Raitakari OT, Reiner AP, Rettig R, Ridker PM, Rivadeneira F, Rossouw JE, Schmidt F, Siscovick D, Soranzo N, Strauch K, Toniolo D, Turner ST, Uitterlinden AG, Ulivi S, Velayutham D, Völker U, Völzke H, Waldenberger M, Wang JJ, Weir DR, Witte D, Kuivaniemi H, Fox CS, Franceschini N, Goessling W, Köttgen A, Chu AY. SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function. J Am Soc Nephrol. 2017 Mar;28(3):981–994.

Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

March 2017

Volume

28

Issue

3

Start / End Page

981 / 994

Location

United States

Related Subject Headings

  • Zebrafish
  • Urology & Nephrology
  • Son of Sevenless Proteins
  • Proto-Oncogene Proteins
  • Protein Tyrosine Phosphatases
  • Kidney
  • Humans
  • Glomerular Filtration Rate
  • Genome-Wide Association Study
  • Genetic Loci