Citations 4
SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function
Li, Man , Weeks, Olivia , Mijatovic, Vladan, Teumer, Alexander , Tromp, Gerard , Fuchsberger, Christian , Gorski, Mathias , Nutile, Teresa , Sedaghat, Sanaz , Sorice, Rossella , Arking, Dan E. , Bihlmeyer, Nathan A. , Böger, Carsten A., Carroll, Robert J. , Cornelis, Marilyn C., Faul, Jessica D. , Feitosa, Mary F. , Gambaro, Giovanni , Gasparini, Paolo , Giulianini, Franco, Heid, Iris M. , Huang, Jinyan , Imboden, Medea , Jeff, Janina M., Jhun, Min A., Katz, Ronit , Kifley, Annette , Kilpeläinen, Tuomas O. , Laakso, Markku , Li‐Gao, Ruifang , Lohman, Kurt, Lu, Yingchang , Mägi, Reedik , Mihailov, Evelin, Mohlke, Karen L. , Mook‐Kanamori, Dennis O. , Robino, Antonietta , Salvi, Erika , Schick, Ursula M., Schulz, Christina‐Alexandra , Smith, Albert V. , Traglia, Michela , Yerges-Armstrong, Laura M. , Goodarzi, Mark O. , Kraja, Aldi T., Wessel, Jennifer , Group,, CHARGE Glycemic-T2D Working, Group,, CHARGE Blood Pressure Working, Boerwinkle, Eric , Borecki, Ingrid B. , Bork‐Jensen, Jette , Böttinger, Erwin P. , Braga, Daniele , Brandslund, Ivan , Brody, Jennifer A. , Carey, David J. , Christensen, Cramer, Crook, Errol D., Boer, Ian H. de , Vries, Aiko P. J. de , Devuyst, Olivier , Dreisbach, Albert W. , Endlich, Karlhans , Franco, Oscar H. , Glümer, Charlotte , Gottesman, Omri, Grarup, Niels , Guðnason, Vilmundur , Harris, Tamara B., Hofman, Albert , Husemoen, Lise Lotte N. , Jackson, Rebecca D. , Jørgensen, Marit E. , Kähönen, Mika , Kardia, Sharon L. R., König, Wolfgang , Kriebel, Jennifer , Lauritzen, Torsten , Lehtimäki, Terho , Levy, Daniel , Linksted, Pamela , Loos, Ruth J. F. , Lupo, Antonio , Meisinger, Christine, Melander, Olle , Mitchell, Paul, Nauck, Matthias, Orho‐Melander, Marju , Parsa, Afshin, Pedersen, Oluf , Peters, Annette , Peters, Ulrike , Polašek, Ozren , Qi, Lu , Reiner, Alex P. , Rettig, Rainer, Ridker, Paul M., Rivadeneira, Fernando , Rossouw, Jacques E. , Schmidt, Frank , Soranzo, Nicole , Strauch, Konstantin , Toniolo, Daniela , Uitterlinden, André G. , Ulivi, Sheila , Velayutham, Dinesh , Völker, Uwe , Völzke, Henry , Waldenberger, Mélanie , Wang, Jie Jin , Weir, David R. , Witte, Daniel R. , Kuivaniemi, Helena , Fox, Caroline S., Franceschini, Nora , Goessling, Wolfram , Köttgen, Anna , Chu, Audrey Y., Rudan, Igor , Vasan, Ramachandran S. , Duijn, Cornelia M. van , Zhao, Wei , Padmanabhan, Sandosh , Lindgren, Cecilia M. , Franks, Paul W. , Weiß, Stefan , Langenberg, Claudia , Hattersley, Andrew T. , Turner, Stephen T. , Li, Yong , Huffman, Jennifer E. , Lyytikäinen, Leo‐Pekka , Tin, Adrienne , Yang, Qiong , Ahluwalia, Tarunveer S. , Chasman, Daniel I. , Dehghan, Abbas , Jackson, Anne , Kumar, Ashish , Malerba, Giovanni , Ruderfer, Douglas , Smith, Jennifer A. , Zhao, Wei , Liu, Chunyu , Group,, CHARGE Glycemic-T2D Working, Group,, CHARGE Blood Pressure Working, Campbell, Archie I , Coresh, Josef , Curhan, Gary C. , Cusi, Daniele , Denny, Joshua C. , Esko, Tõnu , Fülöp, Tibor , Gerhard, Glenn S. , Hansen, Torben , Hayward, Caroline , Hocking, Lynne J. , Hu, Frank B. , Jørgensen, Torben , Kooperberg, Charles , Launer, Lenore J. , Linneberg, Allan , Liu, Ching‐Ti , Meisinger, Christine, Metspalu, Andres , Nürnberg, Peter , Porteous, David John , Probst-Hensch, Nicole M , Psaty, Bruce M. , Raitakari, Olli Tuomas , Siscovick, David S. , Weiss, Stefan , Völker, Uwe , Teumer, Alexander , van Duijn, Cornelia M , Vasan, Ramachandran S , Smith, Albert V , Loos, Ruth J F , Li-Gao, Ruifang , Brody, Jennifer A , Padmanabhan, Sandosh , Levy, Daniel , de Vries, Aiko P J , Devuyst, Olivier; https://orcid.org/0000-0003-3744-4767
Journal of the American Society of Nephrology | December 5, 2016 | Volume: 28 | Issue: 3 | Pages: 981-994
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 <3.7×10 −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.
Polymorphic Variation in TPMT Is the Principal Determinant of TPMT Phenotype: A Meta‐Analysis of Three Genome‐Wide Association Studies
Tamm, R, Mägi, Reedik , Tremmel, Roman , Winter, Stefan , Mihailov, Evelin, Smid, A., Möricke, Anja , Klein, Kathrin , Stanulla, Martin , Houlston, Richard S. , Weinshilboum, Richard M. , Mlinarič‐Raščan, Irena , Milani, Lili , Schwab, Matthias , Schaeffeler, Elke , Tamm, Riin, Schrappe, Martin , Weinshilboum, Richard M. , Metspalu, Andres , Houlston, Richard S , Tremmel, Roman , Schwab, Matthias
Clinical Pharmacology & Therapeutics | October 22, 2016 | Volume: 101 | Issue: 5 | Pages: 684-695
Thiopurine‐related hematotoxicity in pediatric acute lymphoblastic leukemia (ALL) and inflammatory bowel diseases has been linked to genetically defined variability in thiopurine S‐methyltransferase (TPMT) activity. While gene testing of TPMT is being clinically implemented, it is unclear if additional genetic variation influences TPMT activity with consequences for thiopurine‐related toxicity. To examine this possibility, we performed a genome‐wide association study (GWAS) of red blood cell TPMT activity in 844 Estonian individuals and 245 pediatric ALL cases. Additionally, we correlated genome‐wide genotypes to human hepatic TPMT activity in 123 samples. Only genetic variants mapping to chromosome 6, including the TPMT gene region, were significantly associated with TPMT activity ( P < 5.0 × 10 ‐8 ) in each of the three GWAS and a joint meta‐analysis of 1,212 cases (top hit P = 1.2 × 10 ‐72 ). This finding is consistent with TPMT genotype being the primary determinant of TPMT activity, reinforcing the rationale for genetic testing of TPMT alleles in routine clinical practice to individualize mercaptopurine dosage.
Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk
Walsh, Kyle M. , Codd, Veryan , Rice, Terri, Nelson, Christopher P. , Smirnov, Ivan, McCoy, Lucie , Hansen, Helen M. , Elhauge, Edward, Ojha, Juhi, Francis, Stephen , Madsen, Nils R., Bracci, Paige M. , Pico, Alexander R. , Molinaro, Annette M, Tihan, Tarık , Chang, Susan M. , Prados, Michael D. , Jenkins, Robert B. , Wiemels, Joseph L. , Samani, Nilesh J. , Wrensch, Margaret , Duijn, Cornelia M. van , Mägi, Reedik , Prokopenko, Inga , Magnusson, Patrik K. E. , Nyholt, Dale R. , Peters, Annette , Beekman, Marian , Houwing‐Duistermaat, Jeanine J. , Slagboom, P. Eline , Norata, Giuseppe Danilo , Berger, Mitchel S. , Chang, Susan Marina , Wiencke, John K. , van Duijn, Cornelia M , Codd, Veryan , Nelson, Christopher P , Francis, Stephen S , Norata, G Danilo
Oncotarget | December 31, 2015 | Volume: 6 | Issue: 40 | Pages: 42468-42477
Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
Fuchsberger, Christian , Teumer, Alexander , Böger, Carsten A., Endlich, Karlhans , Olden, Matthias , Chen, Ming‐Huei , Li, Man , Gao, Xiaoyi , Gorski, Mathias , Hundertmark, Claudia, Foster, Meredith C., O’Seaghdha, Conall M. , Glazer, Nicole L. , Isaacs, Aaron , Liu, Ching‐Ti , Smith, Albert V. , O’Connell, Jeffrey R. , Struchalin, Maksim , Johnson, Andrew D. , Gierman, Hinco J. , Feitosa, Mary F. , Hwang, Shih-Jen, Atkinson, Elizabeth J. , Lohman, Kurt, Cornelis, Marilyn C., Johansson, Åsa , Tönjes, Anke , Dehghan, Abbas , Lambert, Jean‐Charles , Holliday, Elizabeth G., Sorice, Rossella , Kutalik, Zoltán , Lehtimäki, Terho , Esko, Tõnu , Deshmukh, Harshal , Ulivi, Sheila , Chu, Audrey Y., Murgia, Federico , Trompet, Stella , Imboden, Medea , Coassin, Stefan , Pistis, Giorgio , WTCCC2, Harris, Tamara B., Aspelund, Thor , Eiríksdóttir, Guðný , Mitchell, Braxton D. , Boerwinkle, Eric , Schmidt, Helena , Cavalieri, Margherita, Rao, Madhumathi , Hu, Frank B., Demirkan, Ayşe , Oostra, Ben A., Ding, Jingzhong , Andrews, Jeanette S., Giulianini, Franco, Köenig, Wolfgang , Illig, Thomas, Meisinger, Christa , Gieger, Christian , Zgaga, Lina , Zemunik, Tatijana , Boban, Mladen , Wheeler, Heather E. , Igl, Wilmar , Zaboli, Ghazal, Wright, Alan F., Campbell, Harry, Ellinghaus, David , Nöthlings, Ute , Jacobs, Gunnar, Biffar, Reiner , Ernst, Florian , Kroemer, Heyo K., Stracke, Sylvia , Völker, Uwe , Völzke, Henry , Kovács, Péter , Stümvoll, Michael , Mägi, Reedik , Hofman, Albert , Uitterlinden, André G. , Rivadeneira, Fernando , Aulchenko, Yurii S. , Polašek, Ozren , Hastie, Nick, Vitart, Véronique , Helmer, Catherine , Wang, Jie Jin , Stengel, Bénédicte , Ruggiero, Daniela , Kähönen, Mika , Viikari, Jorma , Nikopensius, Tiit , Province, Michael A. , Ketkar, Shamika , Colhoun, Helen M. , Doney, Alex S. F. , Robino, Antonietta , Krämer, Bernhard K. , Portas, Laura , Ford, Ian, Adam, Martin , Thun, Gian Andri , Paulweber, Bernhard , Haun, Margot, Sala, Cinzia , Mitchell, Paul, Ciullo, Marina , Kim, Stuart K. , Vollenweider, Péter , Raitakari, Olli T., Palmer, Colin, Gasparini, Paolo , Pirastu, Mario, Jukema, J. Wouter , Kronenberg, Florian , Toniolo, Daniela , Guðnason, Vilmundur , Shuldiner, Alan R. , Schmidt, Reinhold, Ferrucci, Luigi , Duijn, Cornelia M. van , Borecki, Ingrid B. , Kardia, Sharon L. R., Rudan, Igor , Pramstaller, Peter P. , Rettig, Rainer, Prokopenko, Inga , Witteman, Jacqueline C.M., Hayward, Caroline , Ridker, Paul M., Parsa, Afshin, Bochud, Murielle , Heid, Iris M. , Kao, W.H. Linda , Fox, Caroline S., Köttgen, Anna , Palmer, Colin N.A. , Chasman, Daniel I. , Pattaro, Cristian , Tin, Adrienne , Taliun, Daniel , Yang, Qiong , Tanaka, Toshiko , Guo, Li , Holliday, Elizabeth G., WTCCC2, Launer, Lenore J. , Andrade, Mariza de , Turner, Stephen T. , Freedman, Barry I. , Minelli, Cosetta , Wild, Sarah H. , Ellinghaus, David , Homuth, Georg , Nauck, Matthias A. , Bergmann, Sven M. , Buckley, Brendan Martin , Metspalu, Andres , Palmer, Colin, Probst-Hensch, Nicole M , Coresh, Josef , Siscovick, David S. , Curhan, Gary C. , Gyllensten, Ulf B , Wilson, James Fox , Franke, André , Palmer, Colin N A , Colhoun, Helen M , Völker, Uwe , Teumer, Alexander , van Duijn, Cornelia M , Smith, Albert V , Mitchell, Braxton D , Shuldiner, Alan R , Ferrucci, Luigi , Koenig, Wolfgang , Kovacs, Peter , Stracke, Sylvia , Liu, Ching-Ti , Wheeler, Heather E , Province, Mike
Human Molecular Genetics | September 8, 2012 | Volume: 21 | Issue: 24 | Pages: 5329-5343