Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
| العنوان: | Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function |
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| المؤلفون: | W. H. Linda Kao, Nicole Probst-Hensch, Florian Ernst, Paul Mitchell, Christa Meisinger, Florian Kronenberg, Sharon L.R. Kardia, Paul M. Ridker, Vilmundur Gudnason, Jeanette S. Andrews, Ming-Huei Chen, Frank B. Hu, Jean-Charles Lambert, Mario Pirastu, Ozren Polasek, Xiaoyi Gao, Sven Bergmann, Catherine Helmer, Wilmar Igl, Jie Jin Wang, Barry I. Freedman, Anke Tönjes, Jacqueline C. M. Witteman, Sheila Ulivi, Conall M. O'Seaghdha, Mika Kähönen, Mariza de Andrade, Daniel I. Chasman, Meredith C. Foster, Rossella Sorice, Mathias Gorski, Eric Boerwinkle, Karlhans Endlich, Maksim Struchalin, Bernhard K. Krämer, Bénédicte Stengel, Caroline Hayward, Giorgio Pistis, Andres Metspalu, Peter Kovacs, Jorma Viikari, Guo Li, Cristian Pattaro, Adrienne Tin, Igor Rudan, Christian Gieger, Mary F. Feitosa, Stephen T. Turner, Gary C. Curhan, Shamika Ketkar, Ian Ford, Peter Vollenweider, Wolfgang Koenig, Madhumathi Rao, Iris M. Heid, Stuart K. Kim, Heather E. Wheeler, Matthias Olden, Hinco J. Gierman, Alex S. F. Doney, Lenore J. Launer, Mladen Boban, Georg Homuth, Paolo Gasparini, Harshal Deshmukh, Henry Völzke, Daniela Ruggiero, Medea Imboden, Elizabeth J. Atkinson, Ben A. Oostra, Stefan Coassin, Ute Nöthlings, Marilyn C. Cornelis, David S. Siscovick, Yongmei Liu, Gian Andri Thun, Gunnar Jacobs, Franco Giulianini, Uwe Völker, Tõnu Esko, Alexander Teumer, Jeffrey R. O'Connell, Brendan M. Buckley, Heyo K. Kroemer, Albert V. Smith, Ulf Gyllensten, Federico Murgia, Man Li, Harry Campbell, Antonietta Robino, Abbas Dehghan, Inga Prokopenko, Shih-Jen Hwang, Sylvia Stracke, Michael Stumvoll, Alan R. Shuldiner, Christian Fuchsberger, Claudia Hundertmark, Luigi Ferrucci, David Ellinghaus, Laura Portas, Caroline S. Fox, Afshin Parsa, Carsten A. Böger, Toshiko Tanaka, Terho Lehtimäki, Ayse Demirkan, James F. Wilson, Elizabeth G. Holliday, Yurii S. Aulchenko, Murielle Bochud, Helen M. Colhoun, Jingzhong Ding, Nicole L. Glazer, Rainer Rettig, Bernhard Paulweber, Margherita Cavalieri, Andre Franke, Ingrid B. Borecki, Olli T. Raitakari, Josef Coresh, Tamara B. Harris, Sarah H. Wild, Reinhold Schmidt, Ching-Ti Liu, Zoltán Kutalik, André G. Uitterlinden, J. Wouter Jukema, Helena Schmidt, Martin Adam, Audrey Y. Chu, Fernando Rivadeneira, Cornelia M. van Duijn, Braxton D. Mitchell, Gudny Eiriksdottir, Tatijana Zemunik, Andrew D. Johnson, Ghazal Zaboli, Reiner Biffar, Thor Aspelund, Cinzia Sala, Peter P. Pramstaller, Veronique Vitart, Michael A. Province, Anna Köttgen, Nicholas D. Hastie, Daniel Taliun, Marina Ciullo, Cosetta Minelli, Kurt Lohman, Matthias Nauck, Thomas Illig, Alan F. Wright, Albert Hofman, Colin N. A. Palmer, Daniela Toniolo, Qiong Yang, Lina Zgaga, Åsa Johansson, Margot Haun, Stella Trompet, Aaron Isaacs, Reedik Mägi, Tiit Nikopensius |
| المساهمون: | Epidemiology, Erasmus School of Social and Behavioural Sciences, Clinical Genetics, Internal Medicine, Chasman, Di, Fuchsberger, C, Pattaro, C, Teumer, A, Böger, Ca, Endlich, K, Olden, M, Chen, Mh, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, Mc, O'Seaghdha, Cm, Glazer, N, Isaacs, A, Liu, Ct, Smith, Av, O'Connell, Jr, Struchalin, M, Tanaka, T, Li, G, Johnson, Ad, Gierman, Hj, Feitosa, Mf, Hwang, Sj, Atkinson, Ej, Lohman, K, Cornelis, Mc, Johansson, A, Tönjes, A, Dehghan, A, Lambert, Jc, Holliday, Eg, Sorice, R, Kutalik, Z, Lehtimäki, T, Esko, T, Deshmukh, H, Ulivi, S, Chu, Ay, Murgia, F, Trompet, S, Imboden, M, Coassin, S, Pistis, G, Cardiogram, Consortium, Icbp, Consortium, the CARe, Consortium, Wtccc2, Harris, Tb, Launer, Lj, Aspelund, T, Eiriksdottir, G, Mitchell, Bd, Boerwinkle, E, Schmidt, H, Cavalieri, M, Rao, M, Hu, F, Demirkan, A, Oostra, Ba, de Andrade, M, Turner, St, Ding, J, Andrews, J, Freedman, Bi, Giulianini, F, Koenig, W, Illig, T, Meisinger, C, Gieger, C, Zgaga, L, Zemunik, T, Boban, M, Minelli, C, Wheeler, He, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Ernst, F, Homuth, G, Kroemer, Hk, Nauck, M, Stracke, S, Völker, U, Völzke, H, Kovacs, P, Stumvoll, M, Mägi, R, Hofman, A, Uitterlinden, Ag, Rivadeneira, F, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, Jj, Stengel, B, Ruggiero, D, Bergmann, S, Kähönen, M, Viikari, J, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Doney, A, Robino, Antonietta, Krämer, Bk, Portas, L, Ford, I, Buckley, Bm, Adam, M, Thun, Ga, Paulweber, B, Haun, M, Sala, C, Mitchell, P, Ciullo, M, Kim, Sk, Vollenweider, P, Raitakari, O, Metspalu, A, Palmer, C, Gasparini, Paolo, Pirastu, M, Jukema, Jw, Probst Hensch, Nm, Kronenberg, F, Toniolo, D, Gudnason, V, Shuldiner, Ar, Coresh, J, Schmidt, R, Ferrucci, L, Siscovick, D, van Duijn, Cm, Borecki, Ib, Kardia, Sl, Liu, Y, Curhan, Gc, Rudan, I, Gyllensten, U, Wilson, Jf, Franke, A, Pramstaller, Pp, Rettig, R, Prokopenko, I, Witteman, J, Hayward, C, Ridker, Pm, Parsa, A, Bochud, M, Heid, Im, Kao, Wl, Fox, C, Köttgen, A. |
| المصدر: | Human Molecular Genetics, 21(24), 5329-5343. Oxford University Press Human Molecular Genetics Human Molecular Genetics; Vol 21 Human Molecular Genetics, 21(24), 5329-5343 Human Molecular Genetics, 21(24), 5329-43. Oxford University Press |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Candidate gene, Amino Acid Transport Systems, Basic/genetics, Genome-wide association study, Gene, Genome, Inhibin-beta Subunits/genetics, GWAS, kidney, eGFR, Genetics (clinical), Inhibin-beta Subunits, Glomerular Filtration Rate/genetics, Genetics, 0303 health sciences, Genetic Predisposition to Disease/genetics, Association Studies Articles, 030305 genetics & heredity, Intracellular Signaling Peptides and Proteins, General Medicine, Low Density Lipoprotein Receptor-Related Protein-2/genetics, Polymorphism, Single Nucleotide/genetics, LRP2, 3. Good health, Low Density Lipoprotein Receptor-Related Protein-2, Genome-Wide Association Study/methods, Single Nucleotide/genetics, Glomerular Filtration Rate, Fusion Regulatory Protein 1, Heavy Chain, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Genome-Wide Association Studies, Humans, SNP, Genetic Predisposition to Disease, ddc:610, Membrane Proteins/genetics, Polymorphism, Molecular Biology, 030304 developmental biology, Genetic association, Fusion Regulatory Protein 1, Heavy Chain/genetics, Fusion Regulatory Protein 1, Genes, Kidney Function, Membrane Proteins, ta3121, Amino Acid Transport Systems, Basic, Amino Acid Transport Systems, Basic/genetics, Heavy Chain/genetics, Intracellular Signaling Peptides and Proteins/genetics, Candidate Disease Gene, Genome-Wide Association Study |
| الوصف: | In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general. |
| وصف الملف: | application/pdf |
| تدمد: | 0964-6906 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c85f6d1aa3bf9ab2abbe237f5fa0e34fTest http://juuli.fi/Record/0252336712Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c85f6d1aa3bf9ab2abbe237f5fa0e34f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09646906 |
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