Медицинская библиотека · PloS one · 2015

Modulation of genetic associations with serum urate levels by body-mass-index in humans.

Huffman Jennifer E, Albrecht Eva, Teumer Alexander, Mangino Massimo, Kapur Karen, Johnson Toby, Kutalik Zoltán, Pirastu Nicola, Pistis Giorgio, Lopez Lorna M, Haller Toomas, Salo Perttu, Goel Anuj, Li Man, Tanaka Toshiko, Dehghan Abbas, 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 Pio, Ulivi Sheila, Vollenweider Peter, Waeber Gerard, Campbell Susan, Kolcic Ivana, Fisher Krista, Viigimaa Margus, 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 Matthias, 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 Nicholas, Campbell Harry, Rudan Igor, Cabrera Claudia, Haley Chris, Franco Oscar H, Merriman Tony R, Gudnason Vilmundur, Pirastu Mario, Penninx Brenda W, Snieder Harold, Metspalu Andres, 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 Markus, Bochud Murielle, Kao W H Linda, Caulfield Mark, Toniolo Daniela, Völzke Henry, Gieger Christian, Köttgen Anna, Vitart Veronique

СтатьяМетаанализПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

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, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, 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.

Для цитирования: Huffman Jennifer E, Albrecht Eva, Teumer Alexander, Mangino Massimo, Kapur Karen, Johnson Toby, Kutalik Zoltán, Pirastu Nicola, Pistis Giorgio, Lopez Lorna M, Haller Toomas, Salo Perttu, Goel Anuj, Li Man, Tanaka Toshiko, Dehghan Abbas, 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 Pio, Ulivi Sheila, Vollenweider Peter, Waeber Gerard, Campbell Susan, Kolcic Ivana, Fisher Krista, Viigimaa Margus, 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 Matthias, 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 Nicholas, Campbell Harry, Rudan Igor, Cabrera Claudia, Haley Chris, Franco Oscar H, Merriman Tony R, Gudnason Vilmundur, Pirastu Mario, Penninx Brenda W, Snieder Harold, Metspalu Andres, 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 Markus, Bochud Murielle, Kao W H Linda, Caulfield Mark, Toniolo Daniela, Völzke Henry, Gieger Christian, Köttgen Anna, Vitart Veronique. Modulation of genetic associations with serum urate levels by body-mass-index in humans.. PloS one. 2015. DOI: 10.1371/journal.pone.0119752.

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