Modulation of genetic associations with serum urate levels by body-mass-index in humans.
Modulation of genetic associations with serum urate levels by body-mass-index in humans.
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DOI：
10.1371/journal.pone.0119752
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Vitart V
中科院分区：
文献类型：
--
作者：
Huffman JE;Albrecht E;Teumer A;Mangino M;Kapur K;Johnson T;Kutalik Z;Pirastu N;Pistis G;Lopez LM;Haller T;Salo P;Goel A;Li M;Tanaka T;Dehghan A;Ruggiero D;Malerba G;Smith AV;Nolte IM;Portas L;Phipps-Green A;Boteva L;Navarro P;Johansson A;Hicks AA;Polasek O;Esko T;Peden JF;Harris SE;Murgia F;Wild SH;Tenesa A;Tin A;Mihailov E;Grotevendt A;Gislason GK;Coresh J;D'Adamo P;Ulivi S;Vollenweider P;Waeber G;Campbell S;Kolcic I;Fisher K;Viigimaa M;Metter JE;Masciullo C;Trabetti E;Bombieri C;Sorice R;Döring A;Reischl E;Strauch K;Hofman A;Uitterlinden AG;Waldenberger M;Wichmann HE;Davies G;Gow AJ;Dalbeth N;Stamp L;Smit JH;Kirin M;Nagaraja R;Nauck M;Schurmann C;Budde K;Farrington SM;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 PB;Hastie N;Campbell H;Rudan I;Cabrera C;Haley C;Franco OH;Merriman TR;Gudnason V;Pirastu M;Penninx BW;Snieder H;Metspalu A;Ciullo M;Pramstaller PP;van Duijn CM;Ferrucci L;Gambaro G;Deary IJ;Dunlop MG;Wilson JF;Gasparini P;Gyllensten U;Spector TD;Wright AF;Hayward C;Watkins H;Perola M;Bochud M;Kao WH;Caulfield M;Toniolo D;Völzke H;Gieger C;Köttgen A;Vitart V
在42569名参与者中，我们测试了身体质量指数（BMI）和影响血清尿酸水平的常见遗传变异之间的相互作用。在精瘦、超重和肥胖个体中进行分层全基因组关联（GWAS）分析，并在非bmi分层总体样本中进行回归型分析。前者没有发现任何具有主要作用的新基因座，但支持了一些已知的和潜在的新的尿酸基因座的调节作用。后者强调RBFOX3的SNP达到全基因组显著水平（效应值0.014,95% CI 0.008-0.02，品特= 2.6 x 10-8）。在相互作用项分析中，RBFOX3和ERO1LB-EDARADD这两个最顶端的基因座也显示出瘦和肥胖阶层之间主效应大小的暗示差异。所有BMI类别间影响差异的前位位点都是新颖的，大多数在阶层间具有较小的影响，但方向相反。它们包括基因座RBMS1-TANK（男性，pdifflean -超重= 4.7 x 10-8），一个与几种肥胖相关特征相关的区域，以及调节脂肪细胞产生的雌二醇的TSPYL5（男性，pdifflean -超重= 9.1 x 10-8）。已知最重要的尿酸基因座是ABCG2，是已知最强的痛风风险基因座，与瘦男性相比，肥胖男性的效果减半（Pdifflean-obese= 2 × 10-4）。最后，途径分析表明n -聚糖生物合成是贫地层中一个重要的尿酸盐相关途径。这些结果说明了一种潜在的有效方法来监测肥胖环境中发生的变化。
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.
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影响因子：
3.7
作者：
Comuzzie AG;Cole SA;Laston SL;Voruganti VS;Haack K;Gibbs RA;Butte NF
通讯作者：
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通讯作者：
Edwards, Todd L.
影响因子：
16.2
作者：
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通讯作者：
Kronenberg F