Human metabolic individuality in biomedical and pharmaceutical research

被引：766

作者：

Suhre, Karsten ^{[1
,2
,3
]}

Shin, So-Youn ^{[4
]}

Petersen, Ann-Kristin ^{[5
]}

Mohney, Robert P. ^{[6
]}

Meredith, David ^{[7
]}

Waegele, Brigitte ^{[1
,8
]}

Altmaier, Elisabeth ^{[1
]}

Deloukas, Panos ^{[4
]}

Erdmann, Jeanette ^{[9
]}

Grundberg, Elin ^{[4
,10
]}

Hammond, Christopher J. ^{[10
]}

Hrabe de Angelis, Martin ^{[11
,12
]}

Kastenmueller, Gabi ^{[1
]}

Koettgen, Anna ^{[13
]}

Kronenberg, Florian ^{[14
]}

Mangino, Massimo ^{[10
]}

Meisinger, Christa ^{[15
]}

Meitinger, Thomas ^{[16
,17
]}

Mewes, Hans-Werner ^{[8
]}

Milburn, Michael V. ^{[6
]}

Prehn, Cornelia ^{[11
]}

Raffler, Johannes ^{[1
,2
]}

Ried, Janina S. ^{[5
]}

Roemisch-Margl, Werner ^{[1
]}

Samani, Nilesh J. ^{[18
,19
]}

Small, Kerrin S. ^{[10
]}

Wichmann, H. -Erich ^{[20
,21
,22
]}

Zhai, Guangju ^{[10
]}

Illig, Thomas ^{[23
]}

Spector, Tim D. ^{[10
]}

Adamski, Jerzy ^{[11
,12
]}

Soranzo, Nicole ^{[4
]}

Gieger, Christian ^{[5
]}

机构：

[1] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, D-85764 Neuherberg, Germany

[2] Univ Munich, Fac Biol, D-82152 Planegg Martinsried, Germany

[3] Qatar Fdn, Weill Cornell Med Coll Qatar, Dept Physiol & Biophys, Doha, Qatar

[4] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England

[5] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany

[6] Metabolon Inc, Res Triangle Pk, NC 27709 USA

[7] Oxford Brookes Univ, Sch Life Sci, Oxford OX3 0BP, England

[8] Tech Univ Munich, Dept Genome Oriented Bioinformat, Life & Food Sci Ctr Weihenstephan, D-85354 Freising Weihenstephan, Germany

[9] Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany

[10] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England

[11] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Genome Anal Ctr, Inst Expt Genet, D-85764 Neuherberg, Germany

[12] Tech Univ Munich, Life & Food Sci Ctr Weihenstephan, Inst Expt Genet, D-85354 Freising Weihenstephan, Germany

[13] Univ Hosp Freiburg, Div Renal, D-79106 Freiburg, Germany

[14] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, A-6020 Innsbruck, Austria

[15] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany

[16] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany

[17] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany

[18] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England

[19] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE1 7RH, Leics, England

[20] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, D-85764 Neuherberg, Germany

[21] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, D-80539 Munich, Germany

[22] Klinikum Grosshadern, D-81377 Munich, Germany

[23] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany

来源：

NATURE | 2011年 / 477卷 / 7362期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; KIDNEY-FUNCTION; LOCI; TRANSPORTER; VARIANTS; METAANALYSIS; CONTRIBUTE; RISK; TOOL;

D O I：

10.1038/nature10354

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.

引用

页码：54 / U60

页数：9

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