Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome: A Multicohort Nontargeted Metabolomics Observational and Mendelian Randomization Study
Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome: A Multicohort Nontargeted Metabolomics Observational and Mendelian Randomization Study
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DOI：
10.2337/db20-1120
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发表时间：
2022-02-01
期刊：
影响因子：
7.7
通讯作者：
Fall, Tove
中科院分区：
文献类型：
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作者：
Ahmad, Shafqat;Hammar, Ulf;Fall, Tove
肥胖与不良的健康结局有关，但代谢影响尚未完全阐明。我们的目的是调查肥胖和循环代谢产物之间的联系，并解决孟德尔随机化(MR)的因果关系。代谢组学数据是通过非靶向超高效液相色谱结合飞行时间质谱仪在三个瑞典人群队列中产生的：ULSAM(N=1,135)，PIVUS(N=970)和Twingene(N=2,059)。我们用210种注解代谢物评估了以BMI衡量的一般肥胖与以BMI调整后的腰臀比(WHRadjBMI)衡量的中心体脂分布之间的关系。我们使用磁共振分析来评估因果效应。最后，我们试图在KORA和TwinsUK队列(N=7,373)、Charge联盟(N=8,631)、Framingham心脏研究(N=2,076)和直接联盟(N=3,029)中复制MR研究结果。在女性和男性中，BMI与77种代谢物相关，而WHRadjBMI与11种代谢物和3种代谢物相关。瑞典队列中的MR分析表明两者之间存在因果关系(P
Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity and circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data were generated with nontargeted ultraperformance liquid chromatography coupled to time-of-flight mass spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N = 1,135), PIVUS (N = 970), and TwinGene (N = 2,059). We assessed associations of general adiposity measured as BMI and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We used MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N = 7,373), the CHARGE Consortium (N = 8,631), the Framingham Heart Study (N = 2,076), and the DIRECT Consortium (N = 3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (P value