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

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Version: Final published version
Serval ID
serval:BIB_E8D96115B4D8
Type
Article: article from journal or magazin.
Collection
Publications
Title
Modulation of genetic associations with serum urate levels by body-mass-index in humans.
Journal
Plos One
Author(s)
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., Caulfield M., Toniolo D., Völzke H., Gieger C., Köttgen A., Vitart V.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
10
Number
3
Pages
e0119752
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
09/04/2015 14:36
Last modification date
20/08/2019 17:11
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