Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans

Show simple item record Huffman, JE en Albrecht, E en Teumer, A en Mangino, M en Kapur, K en Johnson, T en Kutalik, Z en Pirastu, N en Pistis, G en Lopez, LM en Haller, T en Salo, P en Goel, A en Li, M en Tanaka, T en Dehghan, A en Ruggiero, D en Malerba, G en Smith, AV en Nolte, IM en Portas, L en Phipps-Green, A en Boteva, L en Navarro, P en Johansson, A en Hicks, AA en Polasek, O en Esko, T en Peden, JF en Harris, SE en Murgia, F en Wild, SH en Tenesa, A en Tin, A en Mihailov, E en Grotevendt, A en Gislason, GK en Coresh, J en D'Adamo, P en Ulivi, S en Vollenweider, P en Waeber, G en Campbell, S en Kolcic, I en Fisher, K en Viigimaa, M en Metter, JE en Masciullo, C en Trabetti, E en Bombieri, C en Sorice, R en Döring, A en Reischl, E en Strauch, K en Hofman, A en Uitterlinden, AG en Waldenberger, M en Wichmann, HE en Davies, G en Gow, AJ en Dalbeth, Nicola en Stamp, L en Smit, JH en Kirin, M en Nagaraja, R en Nauck, M en Schurmann, C en Budde, K en Farrington, SM en Theodoratou, E en Jula, A en Salomaa, V en Sala, C en Hengstenberg, C en Burnier, M en Mägi, R en Klopp, N en Kloiber, S en Schipf, S en Ripatti, S en Cabras, S en Soranzo, N en Homuth, G en Nutile, T en Munroe, PB en Hastie, N en Campbell, H en Rudan, I en Cabrera, C en Haley, C en Franco, OH en Merriman, TR en Gudnason, V en Pirastu, M en Penninx, BW en Snieder, H en Metspalu, A en Ciullo, M en Pramstaller, PP en van Duijn, CM en Ferrucci, L en Gambaro, G en Deary, IJ en Dunlop, MG en Wilson, JF en Gasparini, P en Gyllensten, U en Spector, TD en Wright, AF en Hayward, C en Watkins, H en Perola, M en Bochud, M en Kao, WH en Caulfield, M en Toniolo, D en Völzke, H en Gieger, C en Köttgen, A en Vitart, V en 2015-07-01T23:49:43Z en 2015 en
dc.identifier.citation PLoS One, 2015, 10 (3), pp. e0119752 - e0119752 en
dc.identifier.issn 1932-6203 en
dc.identifier.uri en
dc.description.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. en
dc.format.medium Electronic-eCollection en
dc.language eng en
dc.publisher Public Library of Science en
dc.relation.ispartofseries PLoS One en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.rights.uri en
dc.title Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans en
dc.type Journal Article en
dc.identifier.doi 10.1371/journal.pone.0119752 en
pubs.issue 3 en
pubs.begin-page e0119752 en
pubs.volume 10 en
dc.description.version VoR - Version of Record en
dc.identifier.pmid 25811787 en
pubs.end-page e0119752 en
dc.rights.accessrights en
pubs.subtype Journal Article en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype Research Support, N.I.H., Extramural en
pubs.subtype Article en
pubs.elements-id 479388 en Medical and Health Sciences en School of Medicine en Medicine Department en
dc.identifier.eissn 1932-6203 en
pubs.record-created-at-source-date 2015-07-02 en
pubs.dimensions-id 25811787 en

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