Li, Man ORCID: 0000-0002-3839-0281, Li, Yong ORCID: 0000-0003-2651-8791, Weeks, Olivia, Mijatovic, Vladan, Teumer, Alexander ORCID: 0000-0002-8309-094X, Huffman, Jennifer E., Tromp, Gerard ORCID: 0000-0002-7761-0806, Fuchsberger, Christian, Gorski, Mathias, Lyytikainen, Leo-Pekka, Nutile, Teresa, Sedaghat, Sanaz, Sorice, Rossella, Tin, Adrienne, Yang, Qiong, Ahluwalia, Tarunveer S., Arking, Dan E., Bihlmeyer, Nathan A., Boeger, Carsten A., Carroll, Robert J., Chasman, Daniel I., Comelis, Marilyn C., Dehghan, Abbas, Faul, Jessica D., Feitosa, Mary F., Gambaro, Giovanni, Gasparini, Paolo ORCID: 0000-0002-0859-0856, Giulianini, Franco, Heid, Iris, Huang, Jinyan, Imboden, Medea, Jackson, Anne U., Jeff, Janina, Jhun, Min A., Katz, Ronit, Kifley, Annette, Kilpelainen, Tuomas ORCID: 0000-0002-8349-3028, Kumar, Ashish, Laakso, Markku, Li-Gao, Ruifang ORCID: 0000-0003-0650-1351, Lohman, Kurt, Lu, Yingchang, Maegi, Reedik, Malerba, Giovanni, Mihailov, Evelin, Mohlke, Karen L., Mook-Kanamori, Dennis O., Robino, Antonietta ORCID: 0000-0003-2152-2353, Ruderfer, Douglas, Salvi, Erika ORCID: 0000-0002-2724-2291, Schick, Ursula M., Schulz, Christina-Alexandra, Smith, Albert V., Smith, Jennifer A., Traglia, Michela, Yerges-Armstrong, Laura M., Zhao, Wei, Goodarzi, Mark O., Kraja, Aldi T., Liu, Chunyu, Wessel, Jennifer ORCID: 0000-0002-7031-0085, Boerwinkle, Eric, Borecki, Ingrid B., Bork-Jensen, Jette, Bottinger, Erwin P., Braga, Daniele ORCID: 0000-0003-2168-8425, Brandslund, Ivan ORCID: 0000-0002-4203-5442, Brody, Jennifer A., Campbell, Archie, Carey, David J., Christensen, Cramer, Coresh, Josef, Crook, Errol, Curhan, Gary C., Cusi, Daniele, de Boer, Ian H., de Vries, Aiko P. J., Denny, Joshua C., Devuyst, Olivier, Dreisbach, Albert W., Endlich, Karlhans ORCID: 0000-0001-6052-6061, Esko, Tonu, Franco, Oscar H., Fulop, Tibor ORCID: 0000-0002-3346-7040, Gerhard, Glenn S., Gluemer, Charlotte, Gottesman, Omri, Grarup, Niels ORCID: 0000-0001-5526-1070, Gudnason, Vilmundur ORCID: 0000-0001-5696-0084, Hansen, Torben, Harris, Tamara B., Hayward, Caroline, Hocking, Lynne, Hofman, Albert, Hu, Frank B., Husemoen, Lise Lotte N., Jackson, Rebecca D., Jorgensen, Torben ORCID: 0000-0001-9453-2830, Jorgensen, Marit E., Kaehoenen, Mika, Kardia, Sharon L. R., Koenig, Wolfgang, Kooperberg, Charles, Kriebel, Jennifer ORCID: 0000-0003-4270-018X, Launer, Lenore J., Lauritzen, Torsten, Lehtimaki, Terho, Levy, Daniel ORCID: 0000-0003-1843-8724, Linksted, Pamela, Linneberg, Allan ORCID: 0000-0002-0994-0184, Liu, Yongmei, Loos, Ruth J. F., Lupo, Antonio, Meisinger, Christine, Melander, Olle, Metspalu, Andres, Mitchell, Paul, Nauck, Matthias, Nuernberg, Peter, Orho-Melander, Marju, Parsa, Afshin, Pedersen, Oluf ORCID: 0000-0002-3321-3972, Peters, Annette ORCID: 0000-0001-6645-0985, Peters, Ulrike, Polasek, Ozren ORCID: 0000-0002-5765-1862, Porteous, David, Probst-Hensch, Nicole M., Psaty, Bruce M., Qi, Lu, Raitakari, Olli T., Reiner, Alex P., Rettig, Rainer, Ridker, Paul M., Rivadeneira, Fernando ORCID: 0000-0001-9435-9441, Rossouw, Jacques E., Schmidt, Frank, Siscovick, David, Soranzo, Nicole, Strauch, Konstantin, Toniolo, Daniela ORCID: 0000-0001-9545-6032, Turner, Stephen T., Uitterlinden, Andre G., Ulivi, Sheila, Velayutham, Dinesh ORCID: 0000-0002-9425-7266, Voelker, Uwe, Volzke, Henry, Waldenberger, Melanie ORCID: 0000-0003-0583-5093, Wang, Jie Jin ORCID: 0000-0001-9491-4898, Weir, David R., Witte, Daniel ORCID: 0000-0002-0769-2922, Kuivaniemi, Helena ORCID: 0000-0001-5753-8766, Fox, Caroline S., Franceschini, Nora, Goessling, Wolfram, Koettgen, Anna and Chu, Audrey Y. (2017). SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function. J. Am. Soc. Nephrol., 28 (3). S. 981 - 995. WASHINGTON: AMER SOC NEPHROLOGY. ISSN 1533-3450

Full text not available from this repository.

Abstract

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 (n(stage1);111,666;n(stage2): 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; P-stage1<3.7 x10(-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=5.4x 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Li, ManUNSPECIFIEDorcid.org/0000-0002-3839-0281UNSPECIFIED
Li, YongUNSPECIFIEDorcid.org/0000-0003-2651-8791UNSPECIFIED
Weeks, OliviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mijatovic, VladanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teumer, AlexanderUNSPECIFIEDorcid.org/0000-0002-8309-094XUNSPECIFIED
Huffman, Jennifer E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tromp, GerardUNSPECIFIEDorcid.org/0000-0002-7761-0806UNSPECIFIED
Fuchsberger, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gorski, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lyytikainen, Leo-PekkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nutile, TeresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sedaghat, SanazUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sorice, RossellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tin, AdrienneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, QiongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahluwalia, Tarunveer S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arking, Dan E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bihlmeyer, Nathan A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boeger, Carsten A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carroll, Robert J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chasman, Daniel I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Comelis, Marilyn C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dehghan, AbbasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Faul, Jessica D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feitosa, Mary F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gambaro, GiovanniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gasparini, PaoloUNSPECIFIEDorcid.org/0000-0002-0859-0856UNSPECIFIED
Giulianini, FrancoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heid, IrisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huang, JinyanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imboden, MedeaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jackson, Anne U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jeff, JaninaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jhun, Min A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Katz, RonitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kifley, AnnetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kilpelainen, TuomasUNSPECIFIEDorcid.org/0000-0002-8349-3028UNSPECIFIED
Kumar, AshishUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laakso, MarkkuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li-Gao, RuifangUNSPECIFIEDorcid.org/0000-0003-0650-1351UNSPECIFIED
Lohman, KurtUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lu, YingchangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maegi, ReedikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malerba, GiovanniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mihailov, EvelinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mohlke, Karen L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mook-Kanamori, Dennis O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robino, AntoniettaUNSPECIFIEDorcid.org/0000-0003-2152-2353UNSPECIFIED
Ruderfer, DouglasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salvi, ErikaUNSPECIFIEDorcid.org/0000-0002-2724-2291UNSPECIFIED
Schick, Ursula M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulz, Christina-AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, Albert V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, Jennifer A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Traglia, MichelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yerges-Armstrong, Laura M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhao, WeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goodarzi, Mark O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kraja, Aldi T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, ChunyuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wessel, JenniferUNSPECIFIEDorcid.org/0000-0002-7031-0085UNSPECIFIED
Boerwinkle, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borecki, Ingrid B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bork-Jensen, JetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bottinger, Erwin P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braga, DanieleUNSPECIFIEDorcid.org/0000-0003-2168-8425UNSPECIFIED
Brandslund, IvanUNSPECIFIEDorcid.org/0000-0002-4203-5442UNSPECIFIED
Brody, Jennifer A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campbell, ArchieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carey, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christensen, CramerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coresh, JosefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Crook, ErrolUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Curhan, Gary C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cusi, DanieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Boer, Ian H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Vries, Aiko P. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denny, Joshua C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Devuyst, OlivierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dreisbach, Albert W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Endlich, KarlhansUNSPECIFIEDorcid.org/0000-0001-6052-6061UNSPECIFIED
Esko, TonuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franco, Oscar H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fulop, TiborUNSPECIFIEDorcid.org/0000-0002-3346-7040UNSPECIFIED
Gerhard, Glenn S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gluemer, CharlotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gottesman, OmriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grarup, NielsUNSPECIFIEDorcid.org/0000-0001-5526-1070UNSPECIFIED
Gudnason, VilmundurUNSPECIFIEDorcid.org/0000-0001-5696-0084UNSPECIFIED
Hansen, TorbenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harris, Tamara B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hayward, CarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hocking, LynneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofman, AlbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hu, Frank B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Husemoen, Lise Lotte N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jackson, Rebecca D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jorgensen, TorbenUNSPECIFIEDorcid.org/0000-0001-9453-2830UNSPECIFIED
Jorgensen, Marit E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaehoenen, MikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kardia, Sharon L. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenig, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kooperberg, CharlesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kriebel, JenniferUNSPECIFIEDorcid.org/0000-0003-4270-018XUNSPECIFIED
Launer, Lenore J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lauritzen, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehtimaki, TerhoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levy, DanielUNSPECIFIEDorcid.org/0000-0003-1843-8724UNSPECIFIED
Linksted, PamelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linneberg, AllanUNSPECIFIEDorcid.org/0000-0002-0994-0184UNSPECIFIED
Liu, YongmeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loos, Ruth J. F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lupo, AntonioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meisinger, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Melander, OlleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Metspalu, AndresUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mitchell, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nauck, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Orho-Melander, MarjuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parsa, AfshinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pedersen, OlufUNSPECIFIEDorcid.org/0000-0002-3321-3972UNSPECIFIED
Peters, AnnetteUNSPECIFIEDorcid.org/0000-0001-6645-0985UNSPECIFIED
Peters, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Polasek, OzrenUNSPECIFIEDorcid.org/0000-0002-5765-1862UNSPECIFIED
Porteous, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Probst-Hensch, Nicole M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Psaty, Bruce M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Qi, LuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raitakari, Olli T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reiner, Alex P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rettig, RainerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ridker, Paul M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rivadeneira, FernandoUNSPECIFIEDorcid.org/0000-0001-9435-9441UNSPECIFIED
Rossouw, Jacques E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siscovick, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soranzo, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strauch, KonstantinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toniolo, DanielaUNSPECIFIEDorcid.org/0000-0001-9545-6032UNSPECIFIED
Turner, Stephen T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uitterlinden, Andre G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ulivi, SheilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Velayutham, DineshUNSPECIFIEDorcid.org/0000-0002-9425-7266UNSPECIFIED
Voelker, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volzke, HenryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waldenberger, MelanieUNSPECIFIEDorcid.org/0000-0003-0583-5093UNSPECIFIED
Wang, Jie JinUNSPECIFIEDorcid.org/0000-0001-9491-4898UNSPECIFIED
Weir, David R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witte, DanielUNSPECIFIEDorcid.org/0000-0002-0769-2922UNSPECIFIED
Kuivaniemi, HelenaUNSPECIFIEDorcid.org/0000-0001-5753-8766UNSPECIFIED
Fox, Caroline S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franceschini, NoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goessling, WolframUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koettgen, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chu, Audrey Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-239201
DOI: 10.1681/ASN.2016020131
Journal or Publication Title: J. Am. Soc. Nephrol.
Volume: 28
Number: 3
Page Range: S. 981 - 995
Date: 2017
Publisher: AMER SOC NEPHROLOGY
Place of Publication: WASHINGTON
ISSN: 1533-3450
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LOW-FREQUENCY; RARE VARIANTS; SEQUENCE VARIANTS; NOONAN SYNDROME; ASSOCIATION; METAANALYSIS; COMMON; DISEASEMultiple languages
Urology & NephrologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23920

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