TY - JOUR
T1 - Modulation of genetic associations with serum urate levels by body-mass-index in humans.
JF - PLoS One
Y1 - 2015
A1 - Huffman, Jennifer E
A1 - Albrecht, Eva
A1 - Teumer, Alexander
A1 - Mangino, Massimo
A1 - Kapur, Karen
A1 - Johnson, Toby
A1 - Kutalik, Zoltán
A1 - Pirastu, Nicola
A1 - Pistis, Giorgio
A1 - Lopez, Lorna M
A1 - Haller, Toomas
A1 - Salo, Perttu
A1 - Goel, Anuj
A1 - Li, Man
A1 - Tanaka, Toshiko
A1 - Dehghan, Abbas
A1 - Ruggiero, Daniela
A1 - Malerba, Giovanni
A1 - Smith, Albert V
A1 - Nolte, Ilja M
A1 - Portas, Laura
A1 - Phipps-Green, Amanda
A1 - Boteva, Lora
A1 - Navarro, Pau
A1 - Johansson, Åsa
A1 - Hicks, Andrew A
A1 - Polasek, Ozren
A1 - Esko, Tõnu
A1 - Peden, John F
A1 - Harris, Sarah E
A1 - Murgia, Federico
A1 - Wild, Sarah H
A1 - Tenesa, Albert
A1 - Tin, Adrienne
A1 - Mihailov, Evelin
A1 - Grotevendt, Anne
A1 - Gislason, Gauti K
A1 - Coresh, Josef
A1 - d'Adamo, Pio
A1 - Ulivi, Sheila
A1 - Vollenweider, Peter
A1 - Waeber, Gerard
A1 - Campbell, Susan
A1 - Kolcic, Ivana
A1 - Fisher, Krista
A1 - Viigimaa, Margus
A1 - Metter, Jeffrey E
A1 - Masciullo, Corrado
A1 - Trabetti, Elisabetta
A1 - Bombieri, Cristina
A1 - Sorice, Rossella
A1 - Döring, Angela
A1 - Reischl, Eva
A1 - Strauch, Konstantin
A1 - Hofman, Albert
A1 - Uitterlinden, André G
A1 - Waldenberger, Melanie
A1 - Wichmann, H-Erich
A1 - Davies, Gail
A1 - Gow, Alan J
A1 - Dalbeth, Nicola
A1 - Stamp, Lisa
A1 - Smit, Johannes H
A1 - Kirin, Mirna
A1 - Nagaraja, Ramaiah
A1 - Nauck, Matthias
A1 - Schurmann, Claudia
A1 - Budde, Kathrin
A1 - Farrington, Susan M
A1 - Theodoratou, Evropi
A1 - Jula, Antti
A1 - Salomaa, Veikko
A1 - Sala, Cinzia
A1 - Hengstenberg, Christian
A1 - Burnier, Michel
A1 - Mägi, Reedik
A1 - Klopp, Norman
A1 - Kloiber, Stefan
A1 - Schipf, Sabine
A1 - Ripatti, Samuli
A1 - Cabras, Stefano
A1 - Soranzo, Nicole
A1 - Homuth, Georg
A1 - Nutile, Teresa
A1 - Munroe, Patricia B
A1 - Hastie, Nicholas
A1 - Campbell, Harry
A1 - Rudan, Igor
A1 - Cabrera, Claudia
A1 - Haley, Chris
A1 - Franco, Oscar H
A1 - Merriman, Tony R
A1 - Gudnason, Vilmundur
A1 - Pirastu, Mario
A1 - Penninx, Brenda W
A1 - Snieder, Harold
A1 - Metspalu, Andres
A1 - Ciullo, Marina
A1 - Pramstaller, Peter P
A1 - van Duijn, Cornelia M
A1 - Ferrucci, Luigi
A1 - Gambaro, Giovanni
A1 - Deary, Ian J
A1 - Dunlop, Malcolm G
A1 - Wilson, James F
A1 - Gasparini, Paolo
A1 - Gyllensten, Ulf
A1 - Spector, Tim D
A1 - Wright, Alan F
A1 - Hayward, Caroline
A1 - Watkins, Hugh
A1 - Perola, Markus
A1 - Bochud, Murielle
A1 - Kao, W H Linda
A1 - Caulfield, Mark
A1 - Toniolo, Daniela
A1 - Völzke, Henry
A1 - Gieger, Christian
A1 - Köttgen, Anna
A1 - Vitart, Veronique
AB - 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.

VL - 10
IS - 3
U1 - http://www.ncbi.nlm.nih.gov/pubmed/25811787?dopt=Abstract
ER -