DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Urate levels in obese individuals. The EFO term obese body mass index status, urate measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: obese body mass index status, urate measurement

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

JE Huffman, E Albrecht, A Teumer, M Mangino, K Kapur, T Johnson, Z Kutalik, N Pirastu, G Pistis, LM Lopez, T Haller, P Salo, A Goel, M Li, T Tanaka, A Dehghan, D Ruggiero, G Malerba, AV Smith, IM Nolte, L Portas, A Phipps-Green, L Boteva, P Navarro, A Johansson, AA Hicks, O Polasek, T Esko, JF Peden, SE Harris, F Murgia, SH Wild, A Tenesa, A Tin, E Mihailov, A Grotevendt, GK Gislason, J Coresh, P D'Adamo, S Ulivi, P Vollenweider, G Waeber, S Campbell, I Kolcic, K Fisher, M Viigimaa, JE Metter, C Masciullo, E Trabetti, C Bombieri, R Sorice, A Döring, E Reischl, K Strauch, A Hofman, AG Uitterlinden, M Waldenberger, HE Wichmann, G Davies, AJ Gow, N Dalbeth, L Stamp, JH Smit, M Kirin, R Nagaraja, M Nauck, C Schurmann, K Budde, SM Farrington, E Theodoratou, A Jula, V Salomaa, C Sala, C Hengstenberg, M Burnier, R Mägi, N Klopp, S Kloiber, S Schipf, S Ripatti, S Cabras, N Soranzo, G Homuth, T Nutile, PB Munroe, N Hastie, H Campbell, I Rudan, C Cabrera, C Haley, OH Franco, TR Merriman, V Gudnason, M Pirastu, BW Penninx, H Snieder, A Metspalu, M Ciullo, PP Pramstaller, CM van Duijn, L Ferrucci, G Gambaro, IJ Deary, MG Dunlop, JF Wilson, P Gasparini, U Gyllensten, TD Spector, AF Wright, C Hayward, H Watkins, M Perola, M Bochud, WH Kao, M Caulfield, D Toniolo, H Völzke, C Gieger, A Köttgen, V Vitart

TITLE:

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

JOURNAL:

PloS one None 2015, Vol 10, pp. e0119752

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: 25811787
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