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Photo: KG Pressfoto

Marju Orho-Melander


Photo: KG Pressfoto

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


  • Man Li
  • Yong Li
  • Olivia Weeks
  • Vladan Mijatovic
  • Alexander Teumer
  • Jennifer E Huffman
  • Gerard Tromp
  • Christian Fuchsberger
  • Mathias Gorski
  • Leo-Pekka Lyytikäinen
  • Teresa Nutile
  • Sanaz Sedaghat
  • Rossella Sorice
  • Adrienne Tin
  • Qiong Yang
  • Tarunveer S Ahluwalia
  • Dan E. Arking
  • Nathan A Bihlmeyer
  • Carsten A Böger
  • Robert J. Carroll
  • Daniel I Chasman
  • Marilyn C. Cornelis
  • Abbas Dehghan
  • Jessica D Faul
  • Mary F Feitosa
  • Giovanni Gambaro
  • Paolo Gasparini
  • Franco Giulianini
  • Iris Heid
  • Jinyan Huang
  • Medea Imboden
  • Anne U Jackson
  • Janina Jeff
  • Min A. Jhun
  • Ronit Katz
  • Annette Kifley
  • Tuomas O Kilpeläinen
  • Ashish Kumar
  • Markku Laakso
  • Ruifang Li-Gao
  • Kurt Lohman
  • Yingchang Lu
  • Reedik Mägi
  • Giovanni Malerba
  • Evelin Mihailov
  • Karen L Mohlke
  • Dennis O. Mook-Kanamori
  • Christina-Alexandra Schulz
  • Olle Melander
  • Marju Orho-Melander

Summary, in English

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.


  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year







Journal of the American Society of Nephrology: JASN





Document type

Journal article


American Society of Nephrology


  • Medical Genetics


  • human genetics
  • kidney development
  • renal function



Research group

  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension


  • ISSN: 1533-3450