Serum uric acid and adiposity: deciphering causality using a bidirectional Mendelian randomization approach.
Serum uric acid and adiposity: deciphering causality using a bidirectional Mendelian randomization approach.
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DOI：
10.1371/journal.pone.0039321
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bochud M
中科院分区：
文献类型：
--
作者：
Lyngdoh T;Vuistiner P;Marques-Vidal P;Rousson V;Waeber G;Vollenweider P;Bochud M
虽然血清尿酸（SUA）与肥胖之间的关系已被确立，但在存在相互矛盾的证据的情况下，因果关系的方向仍不清楚。我们采用双向孟德尔随机化方法，在一项基于人群的研究中，对35 - 75岁的白人进行研究，以探讨SUA和肥胖之间因果关系的性质和方向。我们在一个方向上使用SUA基因SLC 2A 9内的rs6855911作为工具变量，在另一个方向上使用肥胖基因FTO、MC 4 R和TMEM 18内的SNP组合作为工具变量。肥胖指标包括体重、体重指数、腰围和脂肪量。我们应用了两阶段最小二乘回归：第一阶段在我们的仪器上回归SUA/肥胖标志物，第二阶段在第一阶段回归的拟合值上回归感兴趣的响应。SLC 2A 9仪器解释的SUA与脂肪量无关（脂肪量的回归系数[95%置信区间]：0.05 [-0.10，0.19]），而普通最小二乘估计值为0.37 [0.34，0.40]）。相比之下，由FTO、MC 4 R和TMEM 18基因的遗传变异解释的脂肪量与SUA正相关且显著相关（0.31 [0.01，0.62]），与普通最小二乘估计值（0.27 [0.25，0.29]）相似。其他肥胖标志物的结果相似。在成年白种人中使用双向孟德尔随机方法，我们的研究结果表明，SUA升高是肥胖的结果而不是原因。
Although the relationship between serum uric acid (SUA) and adiposity is well established, the direction of the causality is still unclear in the presence of conflicting evidences. We used a bidirectional Mendelian randomization approach to explore the nature and direction of causality between SUA and adiposity in a population-based study of Caucasians aged 35 to 75 years. We used, as instrumental variables, rs6855911 within the SUA gene SLC2A9 in one direction, and combinations of SNPs within the adiposity genes FTO, MC4R and TMEM18 in the other direction. Adiposity markers included weight, body mass index, waist circumference and fat mass. We applied a two-stage least squares regression: a regression of SUA/adiposity markers on our instruments in the first stage and a regression of the response of interest on the fitted values from the first stage regression in the second stage. SUA explained by the SLC2A9 instrument was not associated to fat mass (regression coefficient [95% confidence interval]: 0.05 [−0.10, 0.19] for fat mass) contrasting with the ordinary least square estimate (0.37 [0.34, 0.40]). By contrast, fat mass explained by genetic variants of the FTO, MC4R and TMEM18 genes was positively and significantly associated to SUA (0.31 [0.01, 0.62]), similar to the ordinary least square estimate (0.27 [0.25, 0.29]). Results were similar for the other adiposity markers. Using a bidirectional Mendelian randomization approach in adult Caucasians, our findings suggest that elevated SUA is a consequence rather than a cause of adiposity.
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影响因子：
5.8
作者：
Bochud, Murielle;Marquant, Fabienne;Rousson, Valentin
通讯作者：
Rousson, Valentin
COLAUS研究：一项基于人群的研究，旨在研究心血管危险因素和代谢综合征的流行病学和遗传决定因素。
影响因子：
2.1
作者：
Firmann, Mathieu;Mayor, Vladimir;Vidal, Pedro Marques;Bochud, Murielle;Pecoud, Alain;Hayoz, Daniel;Paccaud, Fred;Preisig, Martin;Song, Kijoung S.;Yuan, Xin;Danoff, Theodore M.;Stirnadel, Heide A.;Waterworth, Dawn;Mooser, Vincent;Waeber, Gerard;Vollenweider, Peter
通讯作者：
Vollenweider, Peter
影响因子：
5.9
作者：
Bhole, Vidula;Choi, Jee Woong J.;Kim, Sung Woo;de Vera, Mary;Choi, Hyon
通讯作者：
Choi, Hyon
影响因子：
16.2
作者：
Brandstätter A;Kiechl S;Kollerits B;Hunt SC;Heid IM;Coassin S;Willeit J;Adams TD;Illig T;Hopkins PN;Kronenberg F
通讯作者：
Kronenberg F
影响因子：
3.5
作者：
Chauhan, Ganesh;Tabassum, Rubina;Bharadwaj, Dwaipayan
通讯作者：
Bharadwaj, Dwaipayan