Crawford, Dana C and Huffman, Jennifer E. and Albrecht, Eva and Teumer, Alexander and Mangino, Massimo and Kapur, Karen and Johnson, Toby and Kutalik, Zoltán and Pirastu, Nicola and Pistis, Giorgio and Lopez, Lorna M. and Haller, Toomas and Salo, Perttu and Goel, Anuj and Li, Man and Tanaka, Toshiko and Dehghan, Abbas and Ruggiero, Daniela and Malerba, Giovanni and Smith, Albert V. and Nolte, Ilja M. and Portas, Laura and Phipps-Green, Amanda and Boteva, Lora and Navarro, Pau and Johansson, Asa and Hicks, Andrew A. and Polasek, Ozren and Esko, Tõnu and Peden, John F. and Harris, Sarah E. and Murgia, Federico and Wild, Sarah H. and Tenesa, Albert and Tin, Adrienne and Mihailov, Evelin and Grotevendt, Anne and Gislason, Gauti K. and Coresh, Josef and D'Adamo, Pio and Ulivi, Sheila and Vollenweider, Peter and Waeber, Gerard and Campbell, Susan and Kolcic, Ivana and Fisher, Krista and Viigimaa, Margus and Metter, Jeffrey E. and Masciullo, Corrado and Trabetti, Elisabetta and Bombieri, Cristina and Sorice, Rossella and Döring, Angela and Reischl, Eva and Strauch, Konstantin and Hofman, Albert and Uitterlinden, Andre G. and Waldenberger, Melanie and Wichmann, H-Erich and Davies, Gail and Gow, Alan J. and Dalbeth, Nicola and Stamp, Lisa and Smit, Johannes H. and Kirin, Mirna and Nagaraja, Ramaiah and Nauck, Matthias and Schurmann, Claudia and Budde, Kathrin and Farrington, Susan M. and Theodoratou, Evropi and Jula, Antti and Salomaa, Veikko and Sala, Cinzia and Hengstenberg, Christian and Burnier, Michel and Mägi, Reedik and Klopp, Norman and Kloiber, Stefan and Schipf, Sabine and Ripatti, Samuli and Cabras, Stefano and Soranzo, Nicole and Homuth, Georg and Nutile, Teresa and Munroe, Patricia B. and Hastie, Nicholas and Campbell, Harry and Rudan, Igor and Cabrera, Claudia and Haley, Chris and Franco, Oscar H. and Merriman, Tony R. and Gudnason, Vilmundur and Pirastu, Mario and Penninx, Brenda W. and Snieder, Harold and Metspalu, Andres and Ciullo, Marina and Pramstaller, Peter P. and van Duijn, Cornelia M. and Ferrucci, Luigi and Gambaro, Giovanni and Deary, Ian J. and Dunlop, Malcolm G. and Wilson, James F. and Gasparini, Paolo and Gyllensten, Ulf and Spector, Tim D. and Wright, Alan F. and Hayward, Caroline and Watkins, Hugh and Perola, Markus and Bochud, Murielle and Kao, W. H. Linda and Caulfield, Mark and Toniolo, Daniela and Völzke, Henry and Gieger, Christian and Köttgen, Anna and Vitart, Veronique (2015) Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans. PLoS ONE, 10 (3). e0119752. ISSN 1932-6203

Preview

Download (516kB) | Preview

Abstract

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.

Item Type:	Article
Keywords:	modulation; Genetic Associations; Serum Urate Levels; body mass index; BMI; Humans;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17240
Identification Number:	https://doi.org/10.1371/journal.pone.0119752
Depositing User:	Lorna Lopez
Date Deposited:	29 May 2023 11:34
Journal or Publication Title:	PLoS ONE
Publisher:	Public Library of Science
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

Repository Staff Only(login required)

Item control page

Downloads

Origin of downloads