Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Nat Genet. 2011 Jun;43(6):565-9. doi: 10.1038/ng.837. Epub 2011 May 15.
We present a genome-wide association study of metabolic traits in human urine, designed to investigate the detoxification capacity of the human body. Using NMR spectroscopy, we tested for associations between 59 metabolites in urine from 862 male participants in the population-based SHIP study. We replicated the results using 1,039 additional samples of the same study, including a 5-year follow-up, and 992 samples from the independent KORA study. We report five loci with joint P values of association from 3.2 × 10(-19) to 2.1 × 10(-182). Variants at three of these loci have previously been linked with important clinical outcomes: SLC7A9 is a risk locus for chronic kidney disease, NAT2 for coronary artery disease and genotype-dependent response to drug toxicity, and SLC6A20 for iminoglycinuria. Moreover, we identify rs37369 in AGXT2 as the genetic basis of hyper-β-aminoisobutyric aciduria.
我们进行了一项针对人体尿液代谢特征的全基因组关联研究，旨在探究人体的解毒能力。我们采用 NMR 光谱法，对来自基于人群的 SHIP 研究中的 862 名男性参与者尿液中的 59 种代谢物进行了关联分析。我们使用相同研究中的另外 1039 个样本进行了重复验证，其中包括 5 年的随访数据，以及来自独立 KORA 研究的 992 个样本。我们报告了五个具有联合 P 值关联的位点，范围从 3.2×10(-19)到 2.1×10(-182)。其中三个位点的变异与重要的临床结果有关：SLC7A9 是慢性肾脏病的风险位点，NAT2 与冠心病和基因型依赖性药物毒性反应有关，SLC6A20 与亚氨基二羧酸尿症有关。此外，我们确定了 AGXT2 中的 rs37369 是高-β-氨基异丁酸尿症的遗传基础。
