Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
| Autor: | Huffman, JE, Albrecht, E, Teumer, A, Mangino, M, Kapur, K, Johnson, T, Kutalik, Z, Pirastu, N, Pistis, G, Lopez, LM, Haller, T, Salo, P, Goel, A, Li, M, Tanaka, T, Dehghan, Abbas, Ruggiero, D, Malerba, G, Smith, AV, Nolte, IM (Ilja), Portas, L, Phipps-Green, A, Boteva, L, Navarro, P, Johansson, A, Hicks, AA, Polasek, O, Esko, T, Peden, JF, Harris, SE, Murgia, F, Wild, SH, Tenesa, A, Tin, A, Mihailov, E, Grotevendt, A, Gislason, GK, Coresh, J, d'Adamo, P, Ulivi, S, Vollenweider, P, Waeber, G, Campbell, S, Kolcic, I, Fisher, K, Viigimaa, M, Metter, JE, Masciullo, C, Trabetti, E, Bombieri, C, Sorice, R, Doring, A, Reischl, E, Strauch, K, Hofman, Bert, Uitterlinden, André, Waldenberger, M, Wichmann, HE, Davies, G, Gow, AJ, Dalbeth, N, Stamp, L, Smit, JH, Kirin, M, Nagaraja, R, Nauck, M, Schurmann, C, Budde, K, Farrington, SM, Theodoratou, E, Jula, A, Salomaa, V, Sala, C, Hengstenberg, C, Burnier, M, Magi, R, Klopp, N, Kloiber, S, Schipf, S, Ripatti, S, Cabras, S, Soranzo, N, Homuth, G, Nutile, T, Munroe, PB, Hastie, N, Campbell, H, Rudan, I, Cabrera, C, Haley, C, Franco Duran, OH, Merriman, TR, Gudnason, V, Pirastu, M, Penninx, BW, Snieder, H, Metspalu, A, Ciullo, M, Pramstaller, PP, Duijn, Cornelia, Ferrucci, L, Gambaro, G, Deary, IJ, Dunlop, MG, Wilson, JF, Gasparini, P, Gyllensten, U, Spector, TD, Wright, AF, Hayward, C, Watkins, H, Perola, M, Bochud, M, Kao, WHL, Caulfield, M, Toniolo, D, Volzke, H, Gieger, C, Kottgen, A, Vitart, V |
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| Přispěvatelé: | Huffman, Jennifer E., Albrecht, Eva, Teumer, Alexander, Mangino, Massimo, Kapur, Karen, Johnson, Toby, Kutalik, Zoltán, Pirastu, Nicola, Pistis, Giorgio, Lopez, Lorna M., Haller, Tooma, Salo, Perttu, Goel, Anuj, Li, Man, Tanaka, Toshiko, Dehghan, Abba, Ruggiero, Daniela, Malerba, Giovanni, Smith, Albert V., Nolte, Ilja M., Portas, Laura, Phipps Green, Amanda, Boteva, Lora, Navarro, Pau, Johansson, Asa, Hicks, Andrew A., Polasek, Ozren, Esko, Tõnu, Peden, John F., Harris, Sarah E., Murgia, Federico, Wild, Sarah H., Tenesa, Albert, Tin, Adrienne, Mihailov, Evelin, Grotevendt, Anne, Gislason, Gauti K., Coresh, Josef, D'Adamo, ADAMO PIO, Ulivi, Sheila, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Kolcic, Ivana, Fisher, Krista, Viigimaa, Margu, Metter, Jeffrey E., Masciullo, Corrado, Trabetti, Elisabetta, Bombieri, Cristina, Sorice, Rossella, Döring, Angela, Reischl, Eva, Strauch, Konstantin, Hofman, Albert, Uitterlinden, Andre G., Waldenberger, Melanie, Wichmann, H. Erich, Davies, Gail, Gow, Alan J., Dalbeth, Nicola, Stamp, Lisa, Smit, Johannes H., Kirin, Mirna, Nagaraja, Ramaiah, Nauck, Matthia, Schurmann, Claudia, Budde, Kathrin, Farrington, Susan M., Theodoratou, Evropi, Jula, Antti, Salomaa, Veikko, Sala, Cinzia, Hengstenberg, Christian, Burnier, Michel, Mägi, Reedik, Klopp, Norman, Kloiber, Stefan, Schipf, Sabine, Ripatti, Samuli, Cabras, Stefano, Soranzo, Nicole, Homuth, Georg, Nutile, Teresa, Munroe, Patricia B., Hastie, Nichola, Campbell, Harry, Rudan, Igor, Cabrera, Claudia, Haley, Chri, Franco, Oscar H., Merriman, Tony R., Gudnason, Vilmundur, Pirastu, Mario, Penninx, Brenda W., Snieder, Harold, Metspalu, Andre, Ciullo, Marina, Pramstaller, Peter P., Van Duijn, Cornelia M., Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J., Dunlop, Malcolm G., Wilson, James F., Gasparini, Paolo, Gyllensten, Ulf, Spector, Tim D., Wright, Alan F., Hayward, Caroline, Watkins, Hugh, Perola, Marku, Bochud, Murielle, Linda Kao, W. H., Caulfield, Mark, Toniolo, Daniela, Völzke, Henry, Gieger, Christian, Köttgen, Anna, Vitart, Veronique, Life Course Epidemiology (LCE), Institute for Molecular Medicine Finland, Samuli Olli Ripatti / Principal Investigator, Biostatistics Helsinki, Quantitative Genetics, Complex Disease Genetics, Epidemiology, Public Health, Internal Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Genetics and Molecular Biology (all)
Male Gout lcsh:Medicine Biochemistry Body Mass Index Risk Factors GWAS ATP Binding Cassette Transporter Subfamily G Member 2 Settore MED/14 - NEFROLOGIA Oxidoreductases Acting on Sulfur Group Donors lcsh:Science METABOLIC SYNDROME INSULIN-RESISTANCE Membrane Glycoproteins PLASMA N-GLYCANS Edar Receptor Medicine (all) Antigens Nuclear Neoplasm Proteins Female Medical Genetics Research Article Genotype Nerve Tissue Proteins Polymorphism Single Nucleotide BMI SDG 3 - Good Health and Well-being Humans Agricultural and Biological Sciences (all) Biochemistry Genetics and Molecular Biology (all) Obesity GENOME-WIDE ASSOCIATION Medicinsk genetik ENVIRONMENT lcsh:R TRANSPORTER serum urate levels genetic associations Overweight Uric Acid ALKALINE-PHOSPHATASE Genetic Loci RISK-FACTORS Linear Models lcsh:Q ATP-Binding Cassette Transporters 3111 Biomedicine URIC-ACID LEVELS Genome-Wide Association Study |
| Zdroj: | Huffman, J E, Albrecht, E, Teumer, A, Mangino, M, Kapur, K, Johnson, T, Kutalik, Z, Pirastu, N, Pistis, G, Lopez, L M, Haller, T, Salo, P, Goel, A, Li, M, Tanaka, T, Dehghan, A, Ruggiero, D, Malerba, G, Smith, A V, Nolte, I M, Portas, L, Phipps-Green, A, Boteva, L, Navarro, P, Johansson, A, Hicks, A A, Polasek, O, Esko, T, Peden, J F, Harris, S E, Murgia, F, Wild, S H, Tenesa, A, Tin, A, Mihailov, E, Grotevendt, A, Gislason, G K, Coresh, J, D'Adamo, P, Ulivi, S, Vollenweider, P, Waeber, G, Campbell, S, Kolcic, I, Fisher, K, Viigimaa, M, Metter, J E, Masciullo, C, Trabetti, E, Bombieri, C, Sorice, R, Döring, A, Reischl, E, Strauch, K, Hofman, A, Uitterlinden, A G, Waldenberger, M, Wichmann, H-E, Davies, G, Gow, A J, Dalbeth, N, Stamp, L, Smit, J H, Kirin, M, Nagaraja, R, Nauck, M, Schurmann, C, Budde, K, Farrington, S M, Theodoratou, E, Jula, A, Salomaa, V, Sala, C, Hengstenberg, C, Burnier, M, Mägi, R, Klopp, N, Kloiber, S, Schipf, S, Ripatti, S, Cabras, S, Soranzo, N, Homuth, G, Nutile, T, Munroe, P B, Hastie, N, Campbell, H, Rudan, I, Cabrera, C, Haley, C, Franco, O H, Merriman, T R, Gudnason, V, Pirastu, M, Penninx, B W, Snieder, H, Metspalu, A, Ciullo, M, Pramstaller, P P, van Duijn, C M, Ferrucci, L, Gambaro, G, Deary, I J, Dunlop, M G, Wilson, J F, Gasparini, P, Gyllensten, U, Spector, T D, Wright, A F, Hayward, C, Watkins, H, Perola, M, Bochud, M, Kao, W H L, Caulfield, M, Toniolo, D, Völzke, H, Gieger, C, Köttgen, A & Vitart, V 2015, ' Modulation of genetic associations with serum urate levels by body-mass-index in humans ', PLoS ONE, vol. 10, no. 3, e0119752 . https://doi.org/10.1371/journal.pone.0119752 PLoS ONE PLoS ONE, 10(3):e0119752. PUBLIC LIBRARY SCIENCE Plos One, vol. 10, no. 3, pp. e0119752 PLoS ONE, Vol 10, Iss 3, p e0119752 (2015) PLOS ONE PLoS One (print), 10(3). Public Library of Science |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0119752 |
| Popis: | We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, P-inter= 2.6 x 10(-8)). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10(-8)), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10(-8)), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10(-4)). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment. |
| Databáze: | OpenAIRE |
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