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
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
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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