Journal
NATURE GENETICS
Volume 43, Issue 6, Pages 565-U97Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.837
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Funding
- German Federal Ministry of Education and Research (BMBF) [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]
- German Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- Siemens Healthcare
- Federal State of Mecklenburg-West Pomerania
- Bruker BioSpin
- Austrian Genome Research Programme
- Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania [03IS2061A]
- Helmholtz Zentrum Munchen-National Research Center for Environmental Health
- German Federal Ministry of Education, Science, Research and Technology
- State of Bavaria
- German National Genome Research Network [NGFNPlus 01GS0823]
- Munich Center of Health Sciences (MC Health) as part of LMUinnovativ
- Deutsche Forschungsgemeinschaft Graduiertenkolleg [GRK 1563]
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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 x 10(-19) to 2.1 x 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-beta-aminoisobutyric aciduria.
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