Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality
Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to spe...
Uloženo v:
| Vydáno v: | PLoS genetics Ročník 11; číslo 9; s. e1005487 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
Public Library of Science
01.09.2015
Public Library of Science (PLoS) |
| Témata: | |
| ISSN: | 1553-7404, 1553-7390, 1553-7404 |
| On-line přístup: | Získat plný text |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blood is a well investigated topic in large mGWAS with over 150 known loci, metabolic detoxification through urinary excretion has only been addressed by few small mGWAS with only 11 associated loci so far. Here we report the largest mGWAS to date, combining targeted and non-targeted 1H NMR analysis of urine samples from 3,861 participants of the SHIP-0 cohort and 1,691 subjects of the KORA F4 cohort. We identified and replicated 22 loci with significant associations with urinary traits, 15 of which are new (HIBCH, CPS1, AGXT, XYLB, TKT, ETNPPL, SLC6A19, DMGDH, SLC36A2, GLDC, SLC6A13, ACSM3, SLC5A11, PNMT, SLC13A3). Two-thirds of the urinary loci also have a metabolite association in blood. For all but one of the 6 loci where significant associations target the same metabolite in blood and urine, the genetic effects have the same direction in both fluids. In contrast, for the SLC5A11 locus, we found increased levels of myo-inositol in urine whereas mGWAS in blood reported decreased levels for the same genetic variant. This might indicate less effective re-absorption of myo-inositol in the kidneys of carriers. In summary, our study more than doubles the number of known loci that influence urinary phenotypes. It thus allows novel insights into the relationship between blood homeostasis and its regulation through excretion. The newly discovered loci also include variants previously linked to chronic kidney disease (CPS1, SLC6A13), pulmonary hypertension (CPS1), and ischemic stroke (XYLB). By establishing connections from gene to disease via metabolic traits our results provide novel hypotheses about molecular mechanisms involved in the etiology of diseases. |
|---|---|
| AbstractList | Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blood is a well investigated topic in large mGWAS with over 150 known loci, metabolic detoxification through urinary excretion has only been addressed by few small mGWAS with only 11 associated loci so far. Here we report the largest mGWAS to date, combining targeted and non-targeted 1H NMR analysis of urine samples from 3,861 participants of the SHIP-0 cohort and 1,691 subjects of the KORA F4 cohort. We identified and replicated 22 loci with significant associations with urinary traits, 15 of which are new (HIBCH, CPS1, AGXT, XYLB, TKT, ETNPPL, SLC6A19, DMGDH, SLC36A2, GLDC, SLC6A13, ACSM3, SLC5A11, PNMT, SLC13A3). Two-thirds of the urinary loci also have a metabolite association in blood. For all but one of the 6 loci where significant associations target the same metabolite in blood and urine, the genetic effects have the same direction in both fluids. In contrast, for the SLC5A11 locus, we found increased levels of myo-inositol in urine whereas mGWAS in blood reported decreased levels for the same genetic variant. This might indicate less effective re-absorption of myo-inositol in the kidneys of carriers. In summary, our study more than doubles the number of known loci that influence urinary phenotypes. It thus allows novel insights into the relationship between blood homeostasis and its regulation through excretion. The newly discovered loci also include variants previously linked to chronic kidney disease (CPS1, SLC6A13), pulmonary hypertension (CPS1), and ischemic stroke (XYLB). By establishing connections from gene to disease via metabolic traits our results provide novel hypotheses about molecular mechanisms involved in the etiology of diseases. Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blood is a well investigated topic in large mGWAS with over 150 known loci, metabolic detoxification through urinary excretion has only been addressed by few small mGWAS with only 11 associated loci so far. Here we report the largest mGWAS to date, combining targeted and non-targeted 1H NMR analysis of urine samples from 3,861 participants of the SHIP-0 cohort and 1,691 subjects of the KORA F4 cohort. We identified and replicated 22 loci with significant associations with urinary traits, 15 of which are new (HIBCH, CPS1, AGXT, XYLB, TKT, ETNPPL, SLC6A19, DMGDH, SLC36A2, GLDC, SLC6A13, ACSM3, SLC5A11, PNMT, SLC13A3). Two-thirds of the urinary loci also have a metabolite association in blood. For all but one of the 6 loci where significant associations target the same metabolite in blood and urine, the genetic effects have the same direction in both fluids. In contrast, for the SLC5A11 locus, we found increased levels of myo-inositol in urine whereas mGWAS in blood reported decreased levels for the same genetic variant. This might indicate less effective re-absorption of myo-inositol in the kidneys of carriers. In summary, our study more than doubles the number of known loci that influence urinary phenotypes. It thus allows novel insights into the relationship between blood homeostasis and its regulation through excretion. The newly discovered loci also include variants previously linked to chronic kidney disease (CPS1, SLC6A13), pulmonary hypertension (CPS1), and ischemic stroke (XYLB). By establishing connections from gene to disease via metabolic traits our results provide novel hypotheses about molecular mechanisms involved in the etiology of diseases. Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blood is a well investigated topic in large mGWAS with over 150 known loci, metabolic detoxification through urinary excretion has only been addressed by few small mGWAS with only 11 associated loci so far. Here we report the largest mGWAS to date, combining targeted and non-targeted ¹H NMR analysis of urine samples from 3,861 participants of the SHIP-0 cohort and 1,691 subjects of the KORA F4 cohort. We identified and replicated 22 loci with significant associations with urinary traits, 15 of which are new (HIBCH, CPS1, AGXT, XYLB, TKT, ETNPPL, SLC6A19, DMGDH, SLC36A2, GLDC, SLC6A13, ACSM3, SLC5A11, PNMT, SLC13A3). Two-thirds of the urinary loci also have a metabolite association in blood. For all but one of the 6 loci where significant associations target the same metabolite in blood and urine, the genetic effects have the same direction in both fluids. In contrast, for the SLC5A11 locus, we found increased levels of myo-inositol in urine whereas mGWAS in blood reported decreased levels for the same genetic variant. This might indicate less effective re-absorption of myo-inositol in the kidneys of carriers. In summary, our study more than doubles the number of known loci that influence urinary phenotypes. It thus allows novel insights into the relationship between blood homeostasis and its regulation through excretion. The newly discovered loci also include variants previously linked to chronic kidney disease (CPS1, SLC6A13), pulmonary hypertension (CPS1), and ischemic stroke (XYLB). By establishing connections from gene to disease via metabolic traits our results provide novel hypotheses about molecular mechanisms involved in the etiology of diseases. Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blood is a well investigated topic in large mGWAS with over 150 known loci, metabolic detoxification through urinary excretion has only been addressed by few small mGWAS with only 11 associated loci so far. Here we report the largest mGWAS to date, combining targeted and non-targeted 1H NMR analysis of urine samples from 3,861 participants of the SHIP-0 cohort and 1,691 subjects of the KORA F4 cohort. We identified and replicated 22 loci with significant associations with urinary traits, 15 of which are new (HIBCH, CPS1, AGXT, XYLB, TKT, ETNPPL, SLC6A19, DMGDH, SLC36A2, GLDC, SLC6A13, ACSM3, SLC5A11, PNMT, SLC13A3). Two-thirds of the urinary loci also have a metabolite association in blood. For all but one of the 6 loci where significant associations target the same metabolite in blood and urine, the genetic effects have the same direction in both fluids. In contrast, for the SLC5A11 locus, we found increased levels of myo-inositol in urine whereas mGWAS in blood reported decreased levels for the same genetic variant. This might indicate less effective re-absorption of myo-inositol in the kidneys of carriers. In summary, our study more than doubles the number of known loci that influence urinary phenotypes. It thus allows novel insights into the relationship between blood homeostasis and its regulation through excretion. The newly discovered loci also include variants previously linked to chronic kidney disease (CPS1, SLC6A13), pulmonary hypertension (CPS1), and ischemic stroke (XYLB). By establishing connections from gene to disease via metabolic traits our results provide novel hypotheses about molecular mechanisms involved in the etiology of diseases. Human metabolism is influenced by genetic and environmental factors defining a person’s metabolic individuality. This individuality is linked to personal differences in the ability to react on metabolic challenges and in the susceptibility to specific diseases. By investigating how common variants in genetic regions (loci) affect individual blood metabolite levels, the substantial contribution of genetic inheritance to metabolic individuality has been demonstrated previously. Meanwhile, more than 150 loci influencing metabolic homeostasis in blood are known. Here we shift the focus to genetic variants that modulate urinary metabolite excretion, for which only 11 loci were reported so far. In the largest genetic study on urinary metabolites to date, we identified 15 additional loci. Most of the 26 loci also affect blood metabolite levels. This shows that the metabolic individuality seen in blood is also reflected in urine, which is expected when urine is regarded as “diluted blood”. Nonetheless, we also found loci that appear to primarily influence metabolite excretion. For instance, we identified genetic variants near a gene of a transporter that change the capability for renal re-absorption of the transporter’s substrate. Thus, our findings could help to elucidate molecular mechanisms influencing kidney function and the body’s detoxification capabilities. |
| Audience | Academic |
| Author | Völzke, Henry Waldenberger, Melanie Arnold, Matthias Bergmann, Sven Raffler, Johannes Friedrich, Nele Altmaier, Elisabeth Kacprowski, Tim Römisch-Margl, Werner Pietzner, Maik Rueedi, Rico Homuth, Georg Strauch, Konstantin Nauck, Matthias Suhre, Karsten Gieger, Christian Wallaschofski, Henri Budde, Kathrin Völker, Uwe Kastenmüller, Gabi |
| AuthorAffiliation | 7 Research Unit Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany 1 Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany 8 Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany 9 Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany 11 Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar 2 Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany 4 Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany 6 Swiss Institute of Bioinformatics, Lausanne, Switzerland 10 Institute for Community Medicine, Uni |
| AuthorAffiliation_xml | – name: 7 Research Unit Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany – name: 11 Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar – name: 3 DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany – name: 5 Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland – name: Stanford University School of Medicine, UNITED STATES – name: 1 Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany – name: 10 Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany – name: 9 Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany – name: 6 Swiss Institute of Bioinformatics, Lausanne, Switzerland – name: 8 Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany – name: 4 Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany – name: 2 Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany |
| Author_xml | – sequence: 1 givenname: Johannes surname: Raffler fullname: Raffler, Johannes – sequence: 2 givenname: Nele surname: Friedrich fullname: Friedrich, Nele – sequence: 3 givenname: Matthias surname: Arnold fullname: Arnold, Matthias – sequence: 4 givenname: Tim surname: Kacprowski fullname: Kacprowski, Tim – sequence: 5 givenname: Rico surname: Rueedi fullname: Rueedi, Rico – sequence: 6 givenname: Elisabeth surname: Altmaier fullname: Altmaier, Elisabeth – sequence: 7 givenname: Sven surname: Bergmann fullname: Bergmann, Sven – sequence: 8 givenname: Kathrin surname: Budde fullname: Budde, Kathrin – sequence: 9 givenname: Christian surname: Gieger fullname: Gieger, Christian – sequence: 10 givenname: Georg surname: Homuth fullname: Homuth, Georg – sequence: 11 givenname: Maik surname: Pietzner fullname: Pietzner, Maik – sequence: 12 givenname: Werner surname: Römisch-Margl fullname: Römisch-Margl, Werner – sequence: 13 givenname: Konstantin surname: Strauch fullname: Strauch, Konstantin – sequence: 14 givenname: Henry surname: Völzke fullname: Völzke, Henry – sequence: 15 givenname: Melanie surname: Waldenberger fullname: Waldenberger, Melanie – sequence: 16 givenname: Henri surname: Wallaschofski fullname: Wallaschofski, Henri – sequence: 17 givenname: Matthias surname: Nauck fullname: Nauck, Matthias – sequence: 18 givenname: Uwe surname: Völker fullname: Völker, Uwe – sequence: 19 givenname: Gabi surname: Kastenmüller fullname: Kastenmüller, Gabi – sequence: 20 givenname: Karsten surname: Suhre fullname: Suhre, Karsten |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26352407$$D View this record in MEDLINE/PubMed |
| BookMark | eNqVk11rFDEUhgdR7If-A9GAIHqxazJJJrNeCKVou9AP6IdehmxyspuSTeokU-2v8C-b7e6WrogoczHDyfO-Obxzzk71OMQAVfWC4CGhgry_in0XlB9eTyEMCcacteJRtU04pwPBMHv84Hur2knpCmPK25F4Wm3VDeU1w2K7-nkAIc5h8NUZQHspRe1UdjGg89ybW_Td5Rm6UN0UMhikgkEnMQzyunByfIaOIatJ9HHudEJjAyE76yAhwgt7Ax4dFU8ULbrsXFDdLTrs5yqsZU6jcTDuxpleeZdvn1VPrPIJnq_eu9Xl508X-4eDo9OD8f7e0UA3ozYPamsxxUpPaM0ZwbxVmICoNdOYNsBs29qRwQ1jZMKEbbSwpJk0WoPghgDFdLd6tfS99jHJVZZJElHjpuZNUxdivCRMVFfyunPz0ryMysm7QuymUnXZaQ8SF1eqKQcuStq0Hikryr2UUCZM25ri9XF1Wz-Zg9ElpE75DdPNk-BmchpvJOMNI6O2GLxdGXTxWw8py7lLGrxXAWK_6JsQzmreLvp-vUSnqrTmgo3FUS9wucco4bQMDy3U8A9UeQyUH1kmzbpS3xC82xAUJsOPPFV9SnJ8fvYf7Mm_s6dfNtk3D9gZKJ9nKfp-MbBpE3z5MO_7oNdzXwC2BHQXU-rA3iMEy8V6rUdCLtZLrtaryD78JtMu3-1LSc_5v4t_AS5_Kh0 |
| CitedBy_id | crossref_primary_10_1002_gepi_22211 crossref_primary_10_1093_cvr_cvy120 crossref_primary_10_1038_s41467_020_20877_8 crossref_primary_10_1038_s41588_019_0504_x crossref_primary_10_1002_gepi_21967 crossref_primary_10_1038_s41564_020_0743_8 crossref_primary_10_3390_metabo12060526 crossref_primary_10_1038_s41467_024_55182_1 crossref_primary_10_1093_bib_bbaf095 crossref_primary_10_1093_ndt_gfy130 crossref_primary_10_1016_j_copbio_2016_10_008 crossref_primary_10_3390_metabo12010061 crossref_primary_10_1073_pnas_2215921119 crossref_primary_10_1016_j_molmet_2018_03_015 crossref_primary_10_1093_ije_dyy287 crossref_primary_10_1186_s12918_018_0579_5 crossref_primary_10_1093_aje_kwx016 crossref_primary_10_3390_ijms17091469 crossref_primary_10_1016_j_aca_2020_10_038 crossref_primary_10_3390_metabo12060512 crossref_primary_10_1210_clinem_dgab544 crossref_primary_10_1016_j_tibs_2018_05_003 crossref_primary_10_1038_s41588_019_0407_x crossref_primary_10_7554_eLife_44941 crossref_primary_10_1016_j_kint_2017_01_007 crossref_primary_10_1038_s41598_017_17107_5 crossref_primary_10_1371_journal_pone_0171324 crossref_primary_10_1016_j_ajhg_2020_09_003 crossref_primary_10_2215_CJN_05780616 crossref_primary_10_1038_s41588_019_0567_8 crossref_primary_10_1016_j_ajhg_2016_03_005 crossref_primary_10_1093_hmg_ddy067 crossref_primary_10_1093_hmg_ddy422 crossref_primary_10_1016_j_ejphar_2025_177725 crossref_primary_10_1681_ASN_2018030291 crossref_primary_10_1038_s42003_020_01583_z crossref_primary_10_1038_s41598_025_07518_0 crossref_primary_10_1186_s12931_024_02720_6 crossref_primary_10_1002_cpz1_70168 crossref_primary_10_1038_ng_3768 crossref_primary_10_1093_ckj_sfy037 crossref_primary_10_1038_s41467_017_01972_9 crossref_primary_10_1038_s41588_018_0135_7 crossref_primary_10_1186_s12864_024_10449_1 crossref_primary_10_1038_s41598_020_72456_y crossref_primary_10_1371_journal_pcbi_1005839 crossref_primary_10_1373_clinchem_2017_275172 crossref_primary_10_3390_metabo13020171 crossref_primary_10_1681_ASN_2017101099 crossref_primary_10_1038_s41598_020_75862_4 crossref_primary_10_1038_s41598_020_78031_9 crossref_primary_10_1093_hmg_ddaa257 crossref_primary_10_1093_ndt_gfy020 crossref_primary_10_1186_s13059_016_1106_x crossref_primary_10_1186_s40246_022_00440_w crossref_primary_10_1007_s11306_025_02296_2 crossref_primary_10_1007_s00011_016_0998_y crossref_primary_10_1038_s41598_020_66334_w crossref_primary_10_1161_CIRCGEN_118_002239 crossref_primary_10_1016_j_semnephrol_2018_01_009 crossref_primary_10_1016_j_arr_2022_101730 crossref_primary_10_1093_jn_nxaa355 crossref_primary_10_1038_ng_3799 crossref_primary_10_1186_s13073_021_00904_z crossref_primary_10_1038_ncomms14357 |
| Cites_doi | 10.1371/journal.pgen.1004835 10.1371/journal.pgen.1004132 10.1371/journal.pgen.1000282 10.1016/S0022-5347(01)62363-2 10.1161/CIRCGENETICS.113.000108 10.1161/CIRCULATIONAHA.113.002251 10.1172/JCI36625 10.1016/j.biopsych.2007.11.010 10.1007/s10654-014-9910-7 10.1186/1471-2105-13-120 10.1093/clinchem/36.10.1717 10.1007/s12035-013-8561-0 10.1371/journal.pone.0088544 10.1093/nar/gkt1113 10.1073/pnas.88.14.6333 10.1093/ije/dyp394 10.1093/nar/gkt1229 10.1074/jbc.M106651200 10.1038/nature12873 10.1111/jon.12020 10.2183/pjab.84.246 10.1038/ng.507 10.1002/humu.21272 10.1093/eurheartj/eht447 10.1093/hmg/ddq062 10.1007/s12263-012-0313-7 10.1016/0006-291X(81)91490-X 10.1093/hmg/ddt239 10.1038/ng1590 10.1371/journal.pgen.1002270 10.1073/pnas.0712038105 10.1186/gm417 10.1006/mgme.2000.3085 10.1186/1471-2105-6-267 10.1074/jbc.M609809200 10.1080/15287390306398 10.1086/500614 10.2337/db12-0876 10.1038/sj.ejhg.5201963 10.1074/jbc.M111.323485 10.1038/nature09270 10.1016/j.cell.2007.04.040 10.1007/s00439-013-1358-4 10.1021/ac504075g 10.1002/humu.22267 10.1038/ng.2797 10.1007/BF03190979 10.1038/nmeth.1785 10.1371/journal.pgen.1000672 10.1074/jbc.M112.427997 10.1371/journal.pgen.1003005 10.1161/01.HYP.0000112424.06921.52 10.1016/S0027-5107(02)00153-7 10.1152/ajpcell.2000.278.5.C1019 10.1038/nature10354 10.1016/j.ymgme.2004.03.007 10.1038/ng.1073 10.1086/519795 10.1021/ac403110u 10.1093/bioinformatics/btu779 10.1016/j.cmet.2013.06.013 10.1038/ng.568 10.1038/jhg.2013.23 10.1152/ajpgi.00422.2007 10.1038/nrg3314 10.1038/ng.687 10.1038/nature11632 10.1093/hmg/ddt519 10.1371/journal.pone.0073076 10.1038/ng.566 10.1007/s00335-010-9253-y 10.1080/10408440601177723 10.1007/BF01659328 10.1371/journal.pgen.1000529 10.1038/ng.2982 10.1371/journal.pgen.1004212 10.1016/j.bbamem.2007.01.007 10.1038/ng1007-1181 10.1038/nchembio.1497 10.1007/BF01324255 10.1161/STROKEAHA.110.598789 10.1093/toxsci/51.1.1 10.1055/s-2005-858235 10.1093/nar/gks1065 10.1371/journal.pgen.1000338 10.1126/science.1260419 10.1016/S0378-1119(02)00416-X 10.1038/ng.837 |
| ContentType | Journal Article |
| Copyright | COPYRIGHT 2015 Public Library of Science 2015 Raffler et al 2015 Raffler et al 2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Raffler J, Friedrich N, Arnold M, Kacprowski T, Rueedi R, Altmaier E, et al. (2015) Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality. PLoS Genet 11(9): e1005487. doi:10.1371/journal.pgen.1005487 |
| Copyright_xml | – notice: COPYRIGHT 2015 Public Library of Science – notice: 2015 Raffler et al 2015 Raffler et al – notice: 2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Raffler J, Friedrich N, Arnold M, Kacprowski T, Rueedi R, Altmaier E, et al. (2015) Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality. PLoS Genet 11(9): e1005487. doi:10.1371/journal.pgen.1005487 |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM IOV ISN ISR 7U8 7X8 C1K JXQ 5PM DOA |
| DOI | 10.1371/journal.pgen.1005487 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Gale In Context: Opposing Viewpoints Gale In Context: Canada Gale In Context: Science TOXLINE MEDLINE - Academic Environmental Sciences and Pollution Management Toxline PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) TOXLINE MEDLINE - Academic Environmental Sciences and Pollution Management |
| DatabaseTitleList | MEDLINE TOXLINE |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology Medicine |
| DocumentTitleAlternate | 15 Novel Loci of Urinary Human Metabolic Individuality |
| EISSN | 1553-7404 |
| EndPage | e1005487 |
| ExternalDocumentID | 1720625662 oai_doaj_org_article_075d3c35e57740329af7b4731347d88d PMC4564198 A431533713 26352407 10_1371_journal_pgen_1005487 |
| Genre | Journal Article |
| GroupedDBID | --- 123 29O 2WC 53G 5VS 7X7 88E 8FE 8FH 8FI 8FJ AAFWJ AAUCC AAWOE AAYXX ABDBF ABUWG ACCTH ACGFO ACIHN ACIWK ACPRK ACUHS ADBBV ADRAZ AEAQA AENEX AFFHD AFKRA AFPKN AHMBA ALMA_UNASSIGNED_HOLDINGS AOIJS B0M BAIFH BAWUL BBNVY BBTPI BCNDV BENPR BHPHI BPHCQ BVXVI BWKFM CCPQU CITATION CS3 DIK DU5 E3Z EAP EAS EBD EBS EJD EMK EMOBN ESX F5P FPL FYUFA GROUPED_DOAJ GX1 HCIFZ HMCUK HYE IAO IGS IHR IHW INH INR IOV ISN ISR ITC KQ8 LK8 M1P M48 M7P O5R O5S OK1 OVT P2P PHGZM PHGZT PIMPY PJZUB PPXIY PQGLB PQQKQ PROAC PSQYO PV9 QF4 QN7 RNS RPM RZL SV3 TR2 TUS UKHRP WOW XSB ~8M 3V. ALIPV C1A CGR CUY CVF ECM EIF H13 IPNFZ M~E NPM RIG WOQ 7U8 7X8 C1K JXQ PUEGO 5PM - AAPBV ABPTK ADACO BBAFP PQEST PQUKI PRINS |
| ID | FETCH-LOGICAL-c698t-2ff030acb32541058a01e72c4c036e4f88f9d06441b47f6c7f16b6cce75d1e303 |
| IEDL.DBID | FPL |
| ISICitedReferencesCount | 74 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000362269000016&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1553-7404 1553-7390 |
| IngestDate | Fri Nov 26 17:13:43 EST 2021 Tue Oct 14 19:03:22 EDT 2025 Tue Nov 04 01:52:08 EST 2025 Fri Sep 05 10:32:41 EDT 2025 Tue Nov 11 10:15:18 EST 2025 Tue Nov 04 17:48:19 EST 2025 Thu Nov 13 14:54:10 EST 2025 Thu Nov 13 14:22:41 EST 2025 Thu Nov 13 15:44:16 EST 2025 Thu May 22 21:23:48 EDT 2025 Wed Feb 19 02:33:54 EST 2025 Sat Nov 29 01:34:04 EST 2025 Tue Nov 18 22:19:01 EST 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 9 |
| Language | English |
| License | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. Creative Commons Attribution License |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c698t-2ff030acb32541058a01e72c4c036e4f88f9d06441b47f6c7f16b6cce75d1e303 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: NF HV HW MN UV GK KSu. Performed the experiments: KB. Analyzed the data: JR MA TK RR GH MP GK KSu. Contributed reagents/materials/analysis tools: EA SB KB CG WRM KSt MW UV. Wrote the paper: JR NF MA TK RR GH MP GK KSu. The authors have declared that no competing interests exist. |
| OpenAccessLink | http://dx.doi.org/10.1371/journal.pgen.1005487 |
| PMID | 26352407 |
| PQID | 1711542582 |
| PQPubID | 23479 |
| ParticipantIDs | plos_journals_1720625662 doaj_primary_oai_doaj_org_article_075d3c35e57740329af7b4731347d88d pubmedcentral_primary_oai_pubmedcentral_nih_gov_4564198 proquest_miscellaneous_1711542582 gale_infotracmisc_A431533713 gale_infotracacademiconefile_A431533713 gale_incontextgauss_ISR_A431533713 gale_incontextgauss_ISN_A431533713 gale_incontextgauss_IOV_A431533713 gale_healthsolutions_A431533713 pubmed_primary_26352407 crossref_primary_10_1371_journal_pgen_1005487 crossref_citationtrail_10_1371_journal_pgen_1005487 |
| PublicationCentury | 2000 |
| PublicationDate | 2015-09-01 |
| PublicationDateYYYYMMDD | 2015-09-01 |
| PublicationDate_xml | – month: 09 year: 2015 text: 2015-09-01 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: San Francisco, CA USA |
| PublicationTitle | PLoS genetics |
| PublicationTitleAlternate | PLoS Genet |
| PublicationYear | 2015 |
| Publisher | Public Library of Science Public Library of Science (PLoS) |
| Publisher_xml | – name: Public Library of Science – name: Public Library of Science (PLoS) |
| References | D McGregor (ref63) 2007; 37 PD Stenson (ref56) 2014; 133 JY Jung (ref34) 2011; 42 D Welter (ref23) 2014; 42 P Roll (ref80) 2002; 285 B Yu (ref25) 2014; 10 M Sabater-Lleal (ref15) 2013; 128 MG Hong (ref16) 2013; 34 JD Figueroa (ref39) 2014; 23 R Aouameur (ref82) 2007; 293 RA Conyers (ref71) 1990; 36 JL Rodríguez-Flores (ref48) 2010; 21 M Arnold (ref51) 2015; 31 T Illig (ref4) 2010; 42 S Bouatra (ref54) 2013; 8 RA Conyers (ref69) 1985; 28 JH Lee (ref67) 2007; 282 S Pekkala (ref77) 2010; 31 RP Holmes (ref70) 1998; 160 L Dai (ref66) 2014; 10 H Magalon (ref41) 2008; 16 S-Y Shin (ref21) 2014; 46 Y Zhang (ref32) 2014; 49 S Bröer (ref35) 2008; 118 GR Abecasis (ref50) 2012; 491 K Lahjouji (ref83) 2007; 1768 I Seppälä (ref20) 2014; 35 G Nicholson (ref5) 2011; 7 Y Okada (ref47) 2014; 506 A Bär (ref68) 1985; 28 A Köttgen (ref26) 2010; 42 S Purcell (ref89) 2007; 81 KP Vatsis (ref43) 1991; 88 M Uhlén (ref52) 2015; 347 PM Groenen (ref81) 2004; 82 J Krumsiek (ref8) 2012; 8 JC Chambers (ref19) 2010; 42 AK Petersen (ref53) 2012; 13 DW Hein (ref40) 2002; 506–507 DM Evans (ref18) 2013; 22 EP Rhee (ref28) 2013; 18 ML Summar (ref31) 2004; 43 T Tanaka (ref3) 2009; 5 A Kittel (ref36) 2014; 9 NM Rao (ref72) 2014; 24 WA Gahl (ref44) 1993 K Suhre (ref6) 2011; 477 J Kettunen (ref7) 2012; 44 T Fujino (ref46) 2001; 276 R Holle (ref86) 2005; 67 K Suhre (ref10) 2011; 43 A Demirkan (ref24) 2015; 11 TM Teslovich (ref37) 2010; 466 JM Benson (ref61) 2003; 66 E Altmaier (ref65) 2014; 29 CK Larive (ref58) 2015; 87 DA Barngrover (ref91) 1981; 102 ME Kleber (ref29) 2013; 6 RD Bunker (ref33) 2013; 288 MD Mailman (ref57) 2007; 39 A Tin (ref27) 2013; 58 A Amberg (ref62) 1999; 51 DS Wishart (ref90) 2013; 41 R Rueedi (ref12) 2014; 10 I Montoliu (ref11) 2013; 8 LA Lange (ref30) 2010; 19 P Landgraf (ref75) 2007; 129 H Wang (ref49) 2000; 278 W Xie (ref14) 2013; 62 M Veiga-da-Cunha (ref59) 2012; 287 J Raffler (ref22) 2013; 5 A Sewer (ref76) 2005; 6 N Rothman (ref38) 2010; 42 U John (ref84) 2001; 46 MJ Landrum (ref55) 2014; 42 M Li (ref64) 2008; 105 G Kikuchi (ref79) 2008; 84 I Bentwich (ref74) 2005; 37 A Alonso (ref13) 2014; 86 O Delaneau (ref87) 2012; 9 C Gieger (ref1) 2008; 4 K Suhre (ref9) 2012; 13 BN Howie (ref88) 2009; 5 E Patin (ref42) 2006; 78 C Bayar (ref73) 1997; 22 AA Hicks (ref2) 2009; 5 K Tomoeda (ref45) 2000; 71 H Völzke (ref85) 2011; 40 CJ Willer (ref17) 2013; 45 L Shao (ref60) 2008; 64 G Kikuchi (ref78) 1973; 1 |
| References_xml | – volume: 11 start-page: e1004835 issue: 1 year: 2015 ident: ref24 article-title: Insight in genome-wide association of metabolite quantitative traits by exome sequence analyses publication-title: PLoS Genetics doi: 10.1371/journal.pgen.1004835 – volume: 10 start-page: e1004132 issue: 2 year: 2014 ident: ref12 article-title: Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links publication-title: PLoS Genetics doi: 10.1371/journal.pgen.1004132 – volume: 4 start-page: e1000282 issue: 11 year: 2008 ident: ref1 article-title: Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum publication-title: PLoS Genetics doi: 10.1371/journal.pgen.1000282 – volume: 160 start-page: 1617 issue: 5 year: 1998 ident: ref70 article-title: Glyoxylate synthesis, and its modulation and influence on oxalate synthesis publication-title: The Journal of Urology doi: 10.1016/S0022-5347(01)62363-2 – volume: 6 start-page: 505 issue: 5 year: 2013 ident: ref29 article-title: Genome-wide association study identifies 3 genomic loci significantly associated with serum levels of homoarginine: the AtheroRemo Consortium publication-title: Circulation Cardiovascular Genetics doi: 10.1161/CIRCGENETICS.113.000108 – volume: 128 start-page: 1310 issue: 12 year: 2013 ident: ref15 article-title: Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.113.002251 – volume: 118 start-page: 3881 issue: 12 year: 2008 ident: ref35 article-title: Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters publication-title: The Journal of Clinical Investigation doi: 10.1172/JCI36625 – volume: 64 start-page: 89 issue: 2 year: 2008 ident: ref60 article-title: Shared gene expression alterations in schizophrenia and bipolar disorder publication-title: Biological Psychiatry doi: 10.1016/j.biopsych.2007.11.010 – volume: 29 start-page: 325 issue: 5 year: 2014 ident: ref65 article-title: Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism publication-title: European Journal of Epidemiology doi: 10.1007/s10654-014-9910-7 – volume: 13 start-page: 120 year: 2012 ident: ref53 article-title: On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome-wide association studies publication-title: BMC Bioinformatics doi: 10.1186/1471-2105-13-120 – volume: 36 start-page: 1717 issue: 10 year: 1990 ident: ref71 article-title: The relation of clinical catastrophes, endogenous oxalate production, and urolithiasis publication-title: Clinical Chemistry doi: 10.1093/clinchem/36.10.1717 – volume: 49 start-page: 852 issue: 2 year: 2014 ident: ref32 article-title: Two Novel Susceptibility SNPs for Ischemic Stroke Using Exome Sequencing in Chinese Han Population publication-title: Molecular Neurobiology doi: 10.1007/s12035-013-8561-0 – volume: 9 start-page: e88544 issue: 2 year: 2014 ident: ref36 article-title: Alanine-glyoxylate aminotransferase 2 (AGXT2) polymorphisms have considerable impact on methylarginine and beta-aminoisobutyrate metabolism in healthy volunteers publication-title: PloS ONE doi: 10.1371/journal.pone.0088544 – volume: 42 start-page: D980 year: 2014 ident: ref55 article-title: ClinVar: public archive of relationships among sequence variation and human phenotype publication-title: Nucleic Acids Research doi: 10.1093/nar/gkt1113 – volume: 88 start-page: 6333 issue: 14 year: 1991 ident: ref43 article-title: Diverse point mutations in the human gene for polymorphic N-acetyltransferase publication-title: Proceedings of the National Academy of Sciences of the United States of America doi: 10.1073/pnas.88.14.6333 – volume: 40 start-page: 294 issue: 2 year: 2011 ident: ref85 article-title: Cohort profile: the study of health in Pomerania publication-title: International Journal of Epidemiology doi: 10.1093/ije/dyp394 – volume: 42 start-page: D1001 year: 2014 ident: ref23 article-title: The NHGRI GWAS Catalog, a curated resource of SNP-trait associations publication-title: Nucleic Acids Research doi: 10.1093/nar/gkt1229 – volume: 276 start-page: 35961 issue: 38 year: 2001 ident: ref46 article-title: Molecular identification and characterization of two medium-chain acyl-CoA synthetases, MACS1 and the Sa gene product publication-title: The Journal of Biological Chemistry doi: 10.1074/jbc.M106651200 – volume: 506 start-page: 376 issue: 7488 year: 2014 ident: ref47 article-title: Genetics of rheumatoid arthritis contributes to biology and drug discovery publication-title: Nature doi: 10.1038/nature12873 – volume: 24 start-page: 411 issue: 4 year: 2014 ident: ref72 article-title: Stroke in primary hyperoxaluria type I publication-title: Journal of Neuroimaging doi: 10.1111/jon.12020 – volume: 84 start-page: 246 issue: 7 year: 2008 ident: ref79 article-title: Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia. publication-title: Proceedings of the Japan Academy Series B, Physical and Biological Sciences doi: 10.2183/pjab.84.246 – volume: 42 start-page: 137 issue: 2 year: 2010 ident: ref4 article-title: A genome-wide perspective of genetic variation in human metabolism publication-title: Nature Genetics doi: 10.1038/ng.507 – volume: 31 start-page: 801 issue: 7 year: 2010 ident: ref77 article-title: Understanding carbamoyl-phosphate synthetase I (CPS1) deficiency by using expression studies and structure-based analysis publication-title: Human Mutation doi: 10.1002/humu.21272 – volume: 35 start-page: 524 issue: 8 year: 2014 ident: ref20 article-title: Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality publication-title: European Heart Journal doi: 10.1093/eurheartj/eht447 – volume: 19 start-page: 2050 issue: 10 year: 2010 ident: ref30 article-title: Genome-wide association study of homocysteine levels in Filipinos provides evidence for CPS1 in women and a stronger MTHFR effect in young adults publication-title: Human Molecular Genetics doi: 10.1093/hmg/ddq062 – volume: 8 start-page: 19 issue: 1 year: 2013 ident: ref11 article-title: Current status on genome-metabolome-wide associations: an opportunity in nutrition research publication-title: Genes & Nutrition doi: 10.1007/s12263-012-0313-7 – volume: 28 start-page: 119 year: 1985 ident: ref68 article-title: Conversion of [U-13C]xylitol and D-[U-13C]glucose into urinary [1,2-13C]glycollate and [1,2-13C]oxalate in man publication-title: International journal for vitamin and nutrition research Supplement = Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Supplement – volume: 102 start-page: 75 issue: 1 year: 1981 ident: ref91 article-title: D-Xylulose-1-phosphate: enzymatic assay and production in isolated rat hepatocytes publication-title: Biochemical and Biophysical Research Communications doi: 10.1016/0006-291X(81)91490-X – volume: 22 start-page: 3998 issue: 19 year: 2013 ident: ref18 article-title: Genome-wide association study identifies loci affecting blood copper, selenium and zinc publication-title: Human Molecular Genetics doi: 10.1093/hmg/ddt239 – volume: 37 start-page: 766 issue: 7 year: 2005 ident: ref74 article-title: Identification of hundreds of conserved and nonconserved human microRNAs publication-title: Nature Genetics doi: 10.1038/ng1590 – volume: 7 start-page: e1002270 issue: 9 year: 2011 ident: ref5 article-title: A genome-wide metabolic QTL analysis in Europeans implicates two loci shaped by recent positive selection publication-title: PLoS Genetics doi: 10.1371/journal.pgen.1002270 – volume: 105 start-page: 2117 issue: 6 year: 2008 ident: ref64 article-title: Symbiotic gut microbes modulate human metabolic phenotypes publication-title: Proceedings of the National Academy of Sciences of the United States of America doi: 10.1073/pnas.0712038105 – volume: 28 start-page: 47 year: 1985 ident: ref69 article-title: A one-compartment model for calcium oxalate tissue deposition during xylitol infusions in humans publication-title: International journal for vitamin and nutrition research Supplement = Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Supplement – volume: 5 start-page: 13 issue: 2 year: 2013 ident: ref22 article-title: Identification and MS-assisted interpretation of genetically influenced NMR signals in human plasma publication-title: Genome Medicine doi: 10.1186/gm417 – volume: 71 start-page: 506 issue: 3 year: 2000 ident: ref45 article-title: Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria publication-title: Molecular Genetics and Metabolism doi: 10.1006/mgme.2000.3085 – volume: 6 start-page: 267 year: 2005 ident: ref76 article-title: Identification of clustered microRNAs using an ab initio prediction method publication-title: BMC Bioinformatics doi: 10.1186/1471-2105-6-267 – volume: 282 start-page: 13419 issue: 18 year: 2007 ident: ref67 article-title: Identification and characterization of the human Set1B histone H3-Lys4 methyltransferase complex publication-title: The Journal of Biological Chemistry doi: 10.1074/jbc.M609809200 – volume: 66 start-page: 1029 issue: 11 year: 2003 ident: ref61 article-title: The uptake, distribution, metabolism, and excretion of methyl tertiary-butyl ether inhaled alone and in combination with gasoline vapor publication-title: Journal of Toxicology and Environmental Health Part A doi: 10.1080/15287390306398 – volume: 78 start-page: 423 issue: 3 year: 2006 ident: ref42 article-title: Deciphering the ancient and complex evolutionary history of human arylamine N-acetyltransferase genes publication-title: American Journal of Human Genetics doi: 10.1086/500614 – volume: 62 start-page: 2141 issue: 6 year: 2013 ident: ref14 article-title: Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes publication-title: Diabetes doi: 10.2337/db12-0876 – volume: 16 start-page: 243 issue: 2 year: 2008 ident: ref41 article-title: Population genetic diversity of the NAT2 gene supports a role of acetylation in human adaptation to farming in Central Asia publication-title: European Journal of Human Genetics: EJHG doi: 10.1038/sj.ejhg.5201963 – volume: 287 start-page: 7246 issue: 10 year: 2012 ident: ref59 article-title: Molecular identification of hydroxylysine kinase and of ammoniophospholyases acting on 5-phosphohydroxy-L-lysine and phosphoethanolamine publication-title: The Journal of Biological Chemistry doi: 10.1074/jbc.M111.323485 – volume: 466 start-page: 707 issue: 7307 year: 2010 ident: ref37 article-title: Biological, clinical and population relevance of 95 loci for blood lipids publication-title: Nature doi: 10.1038/nature09270 – volume: 129 start-page: 1401 issue: 7 year: 2007 ident: ref75 article-title: A mammalian microRNA expression atlas based on small RNA library sequencing publication-title: Cell doi: 10.1016/j.cell.2007.04.040 – volume: 133 start-page: 1 issue: 1 year: 2014 ident: ref56 article-title: The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine publication-title: Human Genetics doi: 10.1007/s00439-013-1358-4 – volume: 87 start-page: 133 issue: 1 year: 2015 ident: ref58 publication-title: Analytical Chemistry doi: 10.1021/ac504075g – volume: 34 start-page: 515 issue: 3 year: 2013 ident: ref16 article-title: A genome-wide assessment of variability in human serum metabolism publication-title: Human Mutation doi: 10.1002/humu.22267 – volume: 45 start-page: 1274 issue: 11 year: 2013 ident: ref17 article-title: Discovery and refinement of loci associated with lipid levels publication-title: Nature Genetics doi: 10.1038/ng.2797 – volume: 22 start-page: 415 issue: 4 year: 1997 ident: ref73 article-title: A study on the route of 1-methylurate formation in theophylline metabolism publication-title: European Journal of Drug Metabolism and Pharmacokinetics doi: 10.1007/BF03190979 – volume: 9 start-page: 179 issue: 2 year: 2012 ident: ref87 article-title: A linear complexity phasing method for thousands of genomes publication-title: Nature Methods doi: 10.1038/nmeth.1785 – volume: 5 start-page: e1000672 issue: 10 year: 2009 ident: ref2 article-title: Genetic determinants of circulating sphingolipid concentrations in European populations publication-title: PLoS Genetics doi: 10.1371/journal.pgen.1000672 – volume: 288 start-page: 1643 issue: 3 year: 2013 ident: ref33 article-title: Structure and function of human xylulokinase, an enzyme with important roles in carbohydrate metabolism publication-title: The Journal of Biological Chemistry doi: 10.1074/jbc.M112.427997 – volume: 8 start-page: e1003005 issue: 10 year: 2012 ident: ref8 article-title: Mining the unknown: a systems approach to metabolite identification combining genetic and metabolic information publication-title: PLoS Genetics doi: 10.1371/journal.pgen.1003005 – volume: 43 start-page: 186 issue: 2 year: 2004 ident: ref31 article-title: Relationship between carbamoyl-phosphate synthetase genotype and systemic vascular function publication-title: Hypertension doi: 10.1161/01.HYP.0000112424.06921.52 – volume: 506–507 start-page: 65 year: 2002 ident: ref40 article-title: Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and carcinogenesis publication-title: Mutation Research doi: 10.1016/S0027-5107(02)00153-7 – volume: 278 start-page: C1019 issue: 5 year: 2000 ident: ref49 article-title: Structure, function, and genomic organization of human Na(+)-dependent high-affinity dicarboxylate transporter publication-title: American journal of physiology Cell Physiology doi: 10.1152/ajpcell.2000.278.5.C1019 – volume: 477 start-page: 54 issue: 7362 year: 2011 ident: ref6 article-title: Human metabolic individuality in biomedical and pharmaceutical research publication-title: Nature doi: 10.1038/nature10354 – volume: 82 start-page: 154 issue: 2 year: 2004 ident: ref81 article-title: Spina bifida and genetic factors related to myo-inositol, glucose, and zinc publication-title: Molecular Genetics and Metabolism doi: 10.1016/j.ymgme.2004.03.007 – volume: 44 start-page: 269 issue: 3 year: 2012 ident: ref7 article-title: Genome-wide association study identifies multiple loci influencing human serum metabolite levels publication-title: Nature Genetics doi: 10.1038/ng.1073 – volume: 81 start-page: 559 issue: 3 year: 2007 ident: ref89 article-title: PLINK: a tool set for whole-genome association and population-based linkage analyses publication-title: American journal of Human Genetics doi: 10.1086/519795 – volume: 86 start-page: 1160 issue: 2 year: 2014 ident: ref13 article-title: Focus: a robust workflow for one-dimensional NMR spectral analysis publication-title: Analytical Chemistry doi: 10.1021/ac403110u – volume: 31 start-page: 1334 issue: 8 year: 2015 ident: ref51 article-title: SNiPA: an interactive, genetic variant-centered annotation browser publication-title: Bioinformatics doi: 10.1093/bioinformatics/btu779 – volume: 18 start-page: 130 issue: 1 year: 2013 ident: ref28 article-title: A genome-wide association study of the human metabolome in a community-based cohort publication-title: Cell Metabolism doi: 10.1016/j.cmet.2013.06.013 – volume: 42 start-page: 376 issue: 5 year: 2010 ident: ref26 article-title: New loci associated with kidney function and chronic kidney disease publication-title: Nature Genetics doi: 10.1038/ng.568 – volume: 58 start-page: 461 issue: 7 year: 2013 ident: ref27 article-title: Using multiple measures for quantitative trait association analyses: application to estimated glomerular filtration rate publication-title: Journal of Human Genetics doi: 10.1038/jhg.2013.23 – volume: 293 start-page: G1300 issue: 6 year: 2007 ident: ref82 article-title: SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine publication-title: American Journal of Physiology—Gastrointestinal and Liver Physiology doi: 10.1152/ajpgi.00422.2007 – volume: 13 start-page: 759 issue: 11 year: 2012 ident: ref9 article-title: Genetic variation in metabolic phenotypes: study designs and applications publication-title: Nature Reviews Genetics doi: 10.1038/nrg3314 – volume: 42 start-page: 978 issue: 11 year: 2010 ident: ref38 article-title: A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci publication-title: Nature Genetics doi: 10.1038/ng.687 – volume: 491 start-page: 56 issue: 7422 year: 2012 ident: ref50 article-title: An integrated map of genetic variation from 1,092 human genomes publication-title: Nature doi: 10.1038/nature11632 – year: 1993 ident: ref44 article-title: GeneReviews(R) – volume: 23 start-page: 1387 issue: 5 year: 2014 ident: ref39 article-title: Genome-wide association study identifies multiple loci associated with bladder cancer risk publication-title: Human Molecular Genetics doi: 10.1093/hmg/ddt519 – volume: 8 start-page: e73076 issue: 9 year: 2013 ident: ref54 article-title: The human urine metabolome publication-title: PloS ONE doi: 10.1371/journal.pone.0073076 – volume: 42 start-page: 373 issue: 5 year: 2010 ident: ref19 article-title: Genetic loci influencing kidney function and chronic kidney disease publication-title: Nature Genetics doi: 10.1038/ng.566 – volume: 21 start-page: 195 issue: 3–4 year: 2010 ident: ref48 article-title: Conserved regulatory motifs at phenylethanolamine N-methyltransferase (PNMT) are disrupted by common functional genetic variation: an integrated computational/experimental approach publication-title: Mammalian Genome doi: 10.1007/s00335-010-9253-y – volume: 37 start-page: 287 issue: 4 year: 2007 ident: ref63 article-title: Ethyl tertiary-butyl ether: a toxicological review publication-title: Critical Reviews in Toxicology doi: 10.1080/10408440601177723 – volume: 1 start-page: 169 issue: 2 year: 1973 ident: ref78 article-title: The glycine cleavage system: composition, reaction mechanism, and physiological significance publication-title: Molecular and Cellular Biochemistry doi: 10.1007/BF01659328 – volume: 5 start-page: e1000529 issue: 6 year: 2009 ident: ref88 article-title: A flexible and accurate genotype imputation method for the next generation of genome-wide association studies publication-title: PLoS Genetics doi: 10.1371/journal.pgen.1000529 – volume: 46 start-page: 543 issue: 6 year: 2014 ident: ref21 article-title: An atlas of genetic influences on human blood metabolites publication-title: Nature Genetics doi: 10.1038/ng.2982 – volume: 10 start-page: e1004212 issue: 3 year: 2014 ident: ref25 article-title: Genetic Determinants Influencing Human Serum Metabolome among African Americans publication-title: . PLoS Genetics doi: 10.1371/journal.pgen.1004212 – volume: 1768 start-page: 1154 issue: 5 year: 2007 ident: ref83 article-title: Expression and functionality of the Na+/myo-inositol cotransporter SMIT2 in rabbit kidney publication-title: Biochimica et Biophysica Acta doi: 10.1016/j.bbamem.2007.01.007 – volume: 39 start-page: 1181 issue: 10 year: 2007 ident: ref57 article-title: The NCBI dbGaP database of genotypes and phenotypes publication-title: Nature Genetics doi: 10.1038/ng1007-1181 – volume: 10 start-page: 365 issue: 5 year: 2014 ident: ref66 article-title: Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark publication-title: Nature Chemical Biology doi: 10.1038/nchembio.1497 – volume: 46 start-page: 186 issue: 3 year: 2001 ident: ref84 article-title: Study of Health In Pomerania (SHIP): a health examination survey in an east German region: objectives and design publication-title: Sozial- und Präventivmedizin doi: 10.1007/BF01324255 – volume: 42 start-page: 1282 issue: 5 year: 2011 ident: ref34 article-title: 1H-NMR-based metabolomics study of cerebral infarction publication-title: Stroke; a journal of cerebral circulation doi: 10.1161/STROKEAHA.110.598789 – volume: 51 start-page: 1 issue: 1 year: 1999 ident: ref62 article-title: Biotransformation and kinetics of excretion of methyl-tert-butyl ether in rats and humans publication-title: Toxicological Sciences doi: 10.1093/toxsci/51.1.1 – volume: 67 start-page: S19 issue: Suppl 1 year: 2005 ident: ref86 article-title: KORA—a research platform for population based health research publication-title: Gesundheitswesen doi: 10.1055/s-2005-858235 – volume: 41 start-page: D801 year: 2013 ident: ref90 article-title: HMDB 3.0—The Human Metabolome Database in 2013 publication-title: Nucleic Acids Research doi: 10.1093/nar/gks1065 – volume: 5 start-page: e1000338 issue: 1 year: 2009 ident: ref3 article-title: Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study publication-title: PLoS Genetics doi: 10.1371/journal.pgen.1000338 – volume: 347 start-page: 1260419 issue: 6220 year: 2015 ident: ref52 article-title: Proteomics. Tissue-based map of the human proteome publication-title: . Science doi: 10.1126/science.1260419 – volume: 285 start-page: 141 issue: 1–2 year: 2002 ident: ref80 article-title: New human sodium/glucose cotransporter gene (KST1): identification, characterization, and mutation analysis in ICCA (infantile convulsions and choreoathetosis) and BFIC (benign familial infantile convulsions) families publication-title: Gene doi: 10.1016/S0378-1119(02)00416-X – volume: 43 start-page: 565 issue: 6 year: 2011 ident: ref10 article-title: A genome-wide association study of metabolic traits in human urine publication-title: Nature Genetics doi: 10.1038/ng.837 |
| SSID | ssj0035897 |
| Score | 2.4571407 |
| Snippet | Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced... Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced... |
| SourceID | plos doaj pubmedcentral proquest gale pubmed crossref |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database Enrichment Source |
| StartPage | e1005487 |
| SubjectTerms | Biomedical research Chromosome Mapping Datasets Funding Gene expression Genetic aspects Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Grants Homeostasis Humans Kidneys Medicine Metabolism Metabolites Metabolomics Methods Nuclear magnetic resonance spectroscopy Proton Magnetic Resonance Spectroscopy Quantitative Trait Loci Studies Urine |
| SummonAdditionalLinks | – databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9QwELbQCiQuiPJqaAGDkDiF5uXYORZEoVIbUGlLb5bj2GWlJVltspX6K_jLzMRJtEFI7YFr8jlSPON52DOfCXnLDbiVIsl8JSLlJ-Bx_SLBU3ihkfCzMKrbzDk_4nkuLi6ybxtXfWFNmKMHdhO3By6tjHXMDINAJYijTFkOX4uxBbIUokTrG_BsSKacDY6ZcNeqMBb7HNL6vmku5uFeL6P3SxAQ1ghgyD5xSh13_2ihZ8tF3fwr_Py7inLDLR08JA_6eJLuu__YIndM9YjcczdMXj8mvz-bqv5l_B_z0tANUVCsH7ymuAtLT7ticFNSVZU0ryu_HR7kxyf02LSgJwtsXm6oa-u1kF3TkAH2yizoEXyT1paerbrWXtodCwzD5poeji1fEPA_IWcHn04_fvH7Oxh8nWai9SNrwQwoXcSQSUIsJlQQGh7pRIPrM4kVwmZlgEEVCMWmmtswLVKtDYgtNOAfn5JZVVdmm1DNWAHBpeFK2yRTRqnYRLpIEhYERmjukXgQgtQ9QTnek7GQ3akbh0TFzalE0cledB7xx1FLR9BxA_4DynfEIr129wCUTvZKJ29SOo-8Qu2Qrld1NBJyH8Ix-EVI_D3ypkMgxUaFNTyXat008vDr-S1A3_PbgE4moHc9yNYwZ1r1zRUw88jvNUHuTpBgTfTk9TYq_DB1jYQAN4AcOU0jj7weFoHEUVidV5l6jRgkdYqYAMwztyjG-UWyI9w18AifLJeJAKZvqvnPjuccmY7CTDz_HxLbIfch1GWuOnCXzNrV2rwgd_VVO29WLzvj8QcF8XDt priority: 102 providerName: Directory of Open Access Journals |
| Title | Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/26352407 https://www.proquest.com/docview/1711542582 https://pubmed.ncbi.nlm.nih.gov/PMC4564198 https://doaj.org/article/075d3c35e57740329af7b4731347d88d http://dx.doi.org/10.1371/journal.pgen.1005487 |
| Volume | 11 |
| WOSCitedRecordID | wos000362269000016&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: DOA dateStart: 20050101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals – providerCode: PRVPQU databaseName: Biological Science Database customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: M7P dateStart: 20050701 isFulltext: true titleUrlDefault: http://search.proquest.com/biologicalscijournals providerName: ProQuest – providerCode: PRVPQU databaseName: Health & Medical Collection customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: 7X7 dateStart: 20050701 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: BENPR dateStart: 20050701 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest – providerCode: PRVPQU databaseName: Publicly Available Content Database customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: PIMPY dateStart: 20050701 isFulltext: true titleUrlDefault: http://search.proquest.com/publiccontent providerName: ProQuest – providerCode: PRVATS databaseName: Public Library of Science (PLoS) Journals Open Access customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: FPL dateStart: 20050701 isFulltext: true titleUrlDefault: http://www.plos.org/publications/ providerName: Public Library of Science |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1bb9MwFLZYB4gXLuOywCgGIfEUyN3O44ZWmNSGqGyje4ocx4FKJamadtJ-BX-Zc5wLy8TEeOlD_LlKjn1uPhcT8pYpUCupF5qCO8L0QOOaqYdReC6x4WeqhD7MOR2zKOKzWRj_cRSvRPBdZn9oaPp-CQTFmD6a2Ftk23GDAJ2tUTxuJa_r85A15XHXzeypH92lv5PFg-WirP5maF7Nl7ykgEYP_vfVH5L7jalJ9-u98YjcUsUOuVNfPnmxQ-5OmrD6Y_LrkyrKn8r8Ns8UvbRgFLMMLyie1dJjnTKuMiqKjEZlYa7bB9FkSidqDbtpgSXOFa2Lf3PwwantA_ZcLegY_pOWOT1Z6QJgqoMH7bS5pEddYRi4BU_Iyejw-ONns7mpwZRByNemk-cgLIRMXfA3wWLjwrIVc6QnQUEqL-c8DzMLTS_YCHkgWW4HaSClYn5mK9CiT8mgKAu1S6j0_RRMUMWEzL1QKCFc5cjU83zLUlwyg7jtAiayaWOOt2ksEh2bY-DO1ORNkOpJQ3WDmN2sZd3G4x_4A9wbHRabcOsHsLxJw9MJWFuZK11f-WBDW64TipzB97lYnZtxnhnkFe6spK5o7URJsg9GG3wis12DvNEIbMRRYKbPd7GpquToy-kNQF-jm4CmPdC7BpSXQDMpmhIMoDx2Aesh93pIkDmyN7yLzNKSrkrADLbAkw4CxyCvWwZKcBbm8BWq3CAGWz85PgfMs5qhOvpiSyQ8WzAI67FabwH6I8X8h-6Gjv2Q7JA_v_6VXpB7YOb6dWbgHhmsVxv1ktyW5-t5tRqSLTZj-pcPyfbBYRRPh_pkZqiFyxCzgWMYiY8m8dlvIwJ27Q |
| linkProvider | Public Library of Science |
| linkToHtml | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9QwELZgeV54lEcDhRqExCklbzvHgihdsRuqsi29WY7jwEpLUm12K_VX8JeZcZyoQVT0wG2VfF7F48fMeGY-E_KGaVAreZS6kgfSjUDjunmEUXiukPAz19Ic5hxPWJbxk5P0wFIKYS2MlSD4iIu6MZF8_FFX-p2VZBs43fFD5nfgnVOQNYb70fq-Tm6wFJQQMj4eTLpNOYx5ymzl3GUtB5rJEPj32_QIP-JvNuifqZQXdNPe_f_YqwfknjVQ6W7b4iG5pqsNcqu9svJ8g9ye2mD8I_Lrk67qn9r9Ni80vTDMFHMTzyme8NKZSTTXBZVVQbO6clfdg2x6SKd6BXNwgYXRDW1Lhkvw3KkfA_ZML-gE_pPWJT1amrJhakIOXbO5ouO-nAycicfkaO_j7MO-a-93cFWS8pUblCVsMVLlIXipYOdx6fmaBSpSoFZ1VHJepoWHBhtMnzJRrPSTPFFKs7jwNejeJ2RUgRA3CVVxnIPhqplUZZRKLWWoA5VHUex5mivmkLAbW6Es-TnewbEQJqLHwAlqxStQ6sJK3SFu3-q0Jf_4B_49Tpsei9Td5gGMuLAjLcBGK0IVxjoGy9sLg1SWDPoXYk1vwXnhkG2cdKKtg-03ILELph50kfmhQ14bBNJ3VJgf9F2um0aMvxxfAfQ1uwrocAB6a0FlDTJT0hZugOSRO2yA3BogYadSg9ebOO070TUCjGcP_O8kCRzyqltbAlth5l-l6zVikDAqiDlgnrZrrZcvEinhiYRD2GAVDgZg-Kaa_zAc6sii5Kf82eWftE3u7M-mEzEZZ5-fk7tgKMdtbuEWGa2Wa_2C3FRnq3mzfGl2mt9n5ojU |
| linkToPdf | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwELbKAhUXHuXRQKEGIXpKm7edY3ksrNgNq9KWXpDlOA6stE2qzW6l_gr-MjPOQw2iohduq2Tsjcfj8Yxn5jMhr5mGbSUNYltyT9oB7Lh2GmAUnisE_Ey1NIc5x2OWJPzkJJ6uke9tLUzDQfAR52VlIvn4oyz0XsPJPcQrqqOnu67P3LbF7hkwHGP-aIK_MYhDeDK2xAKkG-Qmi8GVQRTI6bhV1H7IY9ZU013VUW-3MqD-neoe4If9zS79M73y0n41vPefR3qf3G0MWbpf9_KArOlig9yur7a82CDrkyZo_5D8-qiL8lTb32aZppfEgWIO4wXFk2B6aBLSdUZlkdGkLOxl-yCZHNCJhr-Fjk9nqqJ1aXEOHj51Q6A913M6hj5pmdOjhSkvpiY00TabKTrqys7A6XhEjoYfDt99spt7IGwVxXxpe3kOqkiq1AdvFuxBLh1XM08FCrZfHeSc53HmoGEHYpZHiuVulEZKaRZmroY9-jEZFMDYTUJVGKZg4GomVR7EUkvpa0-lQRA6juaKWcRv51uoBiQd7-qYCxP5Y-As1ewVOAmimQSL2F2rsxok5B_0b1GUOlqE-DYPQApEM_sCbLnMV36oQ7DQHd-LZc5gfD7W_macZxbZRkEUdb1sp6jEPpiEMETm-hZ5ZSgQ5qPAPKIfclVVYvTl-BpEX5PrEB30iHYaorwEninZFHgA51GSe5RbPUrQaKr3ehOXQsu6SoCR7YCfHkWeRV62601gK8wQLHS5QhoElvJCDjRP6vXX8RcBl_DkwiKstzJ7E9B_U8x-Gqx1RFtyY_706k_aJuvT90MxHiWfn5E7YE-HdQriFhksFyv9nNxS58tZtXhhlM9vtMaYCQ |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Genome-wide+association+study+with+targeted+and+non-targeted+NMR+metabolomics+identifies+15+novel+loci+of+urinary+human+metabolic+individuality&rft.jtitle=PLoS+genetics&rft.au=Raffler%2C+Johannes&rft.au=Friedrich%2C+Nele&rft.au=Arnold%2C+Matthias&rft.au=Kacprowski%2C+Tim&rft.date=2015-09-01&rft.pub=Public+Library+of+Science&rft.issn=1553-7390&rft.volume=11&rft.issue=9&rft_id=info:doi/10.1371%2Fjournal.pgen.1005487&rft.externalDBID=ISN&rft.externalDocID=A431533713 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1553-7404&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1553-7404&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1553-7404&client=summon |