@article {12133,
	title = {SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function.},
	journal = {Journal of the American Society of Nephrology },
	volume = {28},
	year = {2017},
	pages = {981-994},
	abstract = {<p>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 (: 111,666; : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (, , and ; <3.7{\texttimes}10), 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,  (=5.4{\texttimes}10 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  and -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.</p>},
	keywords = {Animals, Exome, Genetic Loci, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, kidney, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins, Son of Sevenless Proteins, Zebrafish},
	issn = {1533-3450},
	doi = {10.1681/ASN.2016020131},
	author = {Li, Man and Li, Yong and Weeks, Olivia and Mijatovic, Vladan and Teumer, Alexander and Huffman, Jennifer E and Tromp, Gerard and Fuchsberger, Christian and Gorski, Mathias and Lyytik{\"a}inen, Leo-Pekka and Nutile, Teresa and Sedaghat, Sanaz and Sorice, Rossella and Tin, Adrienne and Yang, Qiong and Ahluwalia, Tarunveer S and Dan E Arking and Bihlmeyer, Nathan A and B{\"o}ger, Carsten A and Carroll, Robert J and Daniel I Chasman and Marilyn C Cornelis and Dehghan, Abbas and Jessica Faul and Feitosa, Mary F and Gambaro, Giovanni and Paolo P. Gasparini and Giulianini, Franco and Iris M Heid and Huang, Jinyan and Imboden, Medea and Jackson, Anne U and Janina Jeff and Jhun, Min A and Katz, Ronit and Kifley, Annette and Kilpel{\"a}inen, Tuomas O and Kumar, Ashish and Laakso, Markku and Li-Gao, Ruifang and Kurt Lohman and Lu, Yingchang and M{\"a}gi, Reedik and Malerba, Giovanni and Mihailov, Evelin and Mohlke, Karen L and Dennis O Mook-Kanamori and Robino, Antonietta and Ruderfer, Douglas and Salvi, Erika and Schick, Ursula M and Schulz, Christina-Alexandra and Smith, Albert V and Smith, Jennifer A and Traglia, Michela and Laura M Yerges-Armstrong and Zhao, Wei and Goodarzi, Mark O and Kraja, Aldi T and Liu, Chunyu and Wessel, Jennifer and Boerwinkle, Eric and Ingrid B Borecki and Bork-Jensen, Jette and Erwin P Bottinger and Braga, Daniele and Brandslund, Ivan and Brody, Jennifer A and Campbell, Archie and Carey, David J and Cramer Christensen and Coresh, Josef and Crook, Errol and Curhan, Gary C and Cusi, Daniele and de Boer, Ian H and de Vries, Aiko P J and Denny, Joshua C and Devuyst, Olivier and Dreisbach, Albert W and Endlich, Karlhans and T{\~o}nu Esko and Franco, Oscar H and Fulop, Tibor and Gerhard, Glenn S and Gl{\"u}mer, Charlotte and Gottesman, Omri and Grarup, Niels and Gudnason, Vilmundur and Hansen, Torben and Tamara B Harris and Caroline Hayward and Lynne J Hocking and Hofman, Albert and Hu, Frank B and Husemoen, Lise Lotte N and Jackson, Rebecca D and J{\o}rgensen, Torben and J{\o}rgensen, Marit E and K{\"a}h{\"o}nen, Mika and Sharon L R Kardia and K{\"o}nig, Wolfgang and Charles Kooperberg and Kriebel, Jennifer and Lenore J Launer and Lauritzen, Torsten and Lehtim{\"a}ki, Terho and Levy, Daniel and Linksted, Pamela and Linneberg, Allan and Liu, Yongmei and Ruth J F Loos and Lupo, Antonio and Meisinger, Christine and Melander, Olle and Andres Metspalu and Mitchell, Paul and Nauck, Matthias and N{\"u}rnberg, Peter and Orho-Melander, Marju and Parsa, Afshin and Pedersen, Oluf and Peters, Annette and Peters, Ulrike and Polasek, Ozren and David J Porteous and Nicole M Probst-Hensch and Psaty, Bruce M and Qi, Lu and Olli T Raitakari and Reiner, Alex P and Rettig, Rainer and Ridker, Paul M and Fernando Rivadeneira and Rossouw, Jacques E and Schmidt, Frank and David S Siscovick and Soranzo, Nicole and Strauch, Konstantin and Toniolo, Daniela and Stephen T Turner and Andr{\'e} G Uitterlinden and Ulivi, Sheila and Velayutham, Dinesh and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Waldenberger, Melanie and Wang, Jie Jin and David R Weir and Daniel Witte and Kuivaniemi, Helena and Caroline S Fox and Franceschini, Nora and Goessling, Wolfram and K{\"o}ttgen, Anna and Chu, Audrey Y}
}
