A genome-wide perspective of genetic variation in human metabolism

被引：507

作者：

Illig, Thomas ^{[2
]}

Gieger, Christian ^{[2
]}

Zhai, Guangju ^{[3
]}

Roemisch-Margl, Werner ^{[1
]}

Wang-Sattler, Rui ^{[2
]}

Prehn, Cornelia ^{[4
]}

Altmaier, Elisabeth ^{[1
,5
]}

Kastenmueller, Gabi ^{[1
]}

Kato, Bernet S. ^{[3
]}

Mewes, Hans-Werner ^{[1
,6
]}

Meitinger, Thomas ^{[7
,8
]}

de Angelis, Martin Hrabe ^{[4
,9
]}

Kronenberg, Florian ^{[10
]}

Soranzo, Nicole ^{[3
,11
]}

Wichmann, H-Erich ^{[2
,12
,13
]}

Spector, Tim D. ^{[3
]}

Adamski, Jerzy ^{[4
,9
]}

Suhre, Karsten ^{[1
,5
]}

机构：

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

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

[3] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[4] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Expt Genet, Genome Anal Ctr, Neuherberg, Germany

[5] Univ Munich, Fac Biol, Planegg Martinsried, Germany

[6] Tech Univ Munich, Dept Genome Oriented Bioinformat, Life & Food Sci Ctr Weihenstephan, D-8050 Freising Weihenstephan, Germany

[7] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany

[8] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany

[9] Tech Univ Munich, Life & Food Sci Ctr Weihenstephan, Inst Human Genet, D-8050 Freising Weihenstephan, Germany

[10] Innsbruck Med Univ, Div Genet Epidemiol, Dept Med Genet Mol & Clin Pharmacol, Innsbruck, Austria

[11] Wellcome Trust Sanger Inst, Hinxton, England

[12] Univ Munich, Inst Med Informa ,Biometry & Epidemiol, Munich, Germany

[13] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany

来源：

NATURE GENETICS | 2010年 / 42卷 / 02期

基金：

美国国家卫生研究院; 英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

FASTING GLUCOSE; POPULATION; LOCI; ASSOCIATION; DISEASE; VARIANTS; RISK; METABOLOMICS; POLYMORPHISM; FREQUENCY;

D O I：

10.1038/ng.507

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Serum metabolite concentrations provide a direct readout of biological processes in the human body, and they are associated with disorders such as cardiovascular and metabolic diseases. We present a genome-wide association study (GWAS) of 163 metabolic traits measured in human blood from 1,809 participants from the KORA population, with replication in 422 participants of the TwinsUK cohort. For eight out of nine replicated loci (FADS1, ELOVL2, ACADS, ACADM, ACADL, SPTLC3, ETFDH and SLC16A9), the genetic variant is located in or near genes encoding enzymes or solute carriers whose functions match the associating metabolic traits. In our study, the use of metabolite concentration ratios as proxies for enzymatic reaction rates reduced the variance and yielded robust statistical associations with P values ranging from 3 x 10(-24) to 6.5 x 10(-179). These loci explained 5.6%-36.3% of the observed variance in metabolite concentrations. For several loci, associations with clinically relevant parameters have been reported previously.

引用

页码：137 / U66

页数：7

共 27 条

[1] Bioinformatics analysis of targeted metabolomics - Uncovering old and new tales of diabetic mice under medication
Altmaier, Elisabeth
Ramsay, Steven L.
Graber, Armin
Mewes, Hans-Werner
Weinberger, Klaus M.
Suhre, Karsten
[J]. ENDOCRINOLOGY, 2008, 149 (07) : 3478 - 3489
[2] Andrew T, 2001, Twin Res, V4, P464, DOI 10.1375/1369052012803
[3] Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
Aulchenko, Yurii S.
Ripatti, Samuli
Lindqvist, Ida
Boomsma, Dorret
Heid, Iris M.
Pramstaller, Peter P.
Penninx, Brenda W. J. H.
Janssens, A. Cecile J. W.
Wilson, James F.
Spector, Tim
Martin, Nicholas G.
Pedersen, Nancy L.
Kyvik, Kirsten Ohm
Kaprio, Jaakko
Hofman, Albert
Freimer, Nelson B.
Jarvelin, Marjo-Riitta
Gyllensten, Ulf
Campbell, Harry
Rudan, Igor
Johansson, Asa
Marroni, Fabio
Hayward, Caroline
Vitart, Veronique
Jonasson, Inger
Pattaro, Cristian
Wright, Alan
Hastie, Nick
Pichler, Irene
Hicks, Andrew A.
Falchi, Mario
Willemsen, Gonneke
Hottenga, Jouke-Jan
de Geus, Eco J. C.
Montgomery, Grant W.
Whitfield, John
Magnusson, Patrik
Saharinen, Juha
Perola, Markus
Silander, Kaisa
Isaacs, Aaron
Sijbrands, Eric J. G.
Uitterlinden, Andre G.
Witteman, Jacqueline C. M.
Oostra, Ben A.
Elliott, Paul
Ruokonen, Aimo
Sabatti, Chiara
Gieger, Christian
Meitinger, Thomas
[J]. NATURE GENETICS, 2009, 41 (01) : 47 - 55
[4] Association of fatty acid desaturase genes with attention-deficit/hyperactivity disorder
Brookes, Keeley J.
Chen, Wai
Xu, Xiaohui
Taylor, Eric
Asherson, Philip
[J]. BIOLOGICAL PSYCHIATRY, 2006, 60 (10) : 1053 - 1061
[5] Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism
Caspi, Avshalom
Williams, Benjamin
Kim-Cohen, Julia
Craig, Ian W.
Milne, Barry J.
Poulton, Richie
Schalkwyk, Leonard C.
Taylor, Alan
Werts, Helen
Moffitt, Terrie E.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (47) : 18860 - 18865
[6] Thermolabile phenotype of carnitine palmitoyltransferase II variations as a predisposing factor for influenza-associated encephalopathy
Chen, Y
Mizuguchi, H
Yao, D
Ide, M
Kuroda, Y
Shigematsu, Y
Yamaguchi, S
Yamaguchi, M
Kinoshita, M
Kido, H
[J]. FEBS LETTERS, 2005, 579 (10): : 2040 - 2044
[7] Genetics Meets Metabolomics: A Genome-Wide Association Study of Metabolite Profiles in Human Serum
Gieger, Christian
Geistlinger, Ludwig
Altmaier, Elisabeth
de Angelis, Martin Hrabe
Kronenberg, Florian
Meitinger, Thomas
Mewes, Hans-Werner
Wichmann, H. -Erich
Weinberger, Klaus M.
Adamski, Jerzy
Illig, Thomas
Suhre, Karsten
[J]. PLOS GENETICS, 2008, 4 (11)
[8] Identification of four new mutations in the short-chain acyl-CoA dehydrogenase (SCAD) gene in two patients:: one of the variant alleles, 511C→T, is present at an unexpectedly high frequency in the general population, as was the case for 625G→A, together conferring susceptibility to ethylmalonic aciduria
Gregersen, N
Winter, VS
Corydon, MJ
Corydon, TJ
Rinaldo, P
Ribes, A
Martinez, G
Bennett, MJ
Vianey-Saban, C
Bhala, A
Hale, DE
Lehnert, W
Kmoch, S
Roig, M
Riudor, E
Eiberg, H
Andresen, BS
Bross, P
Bolund, LA
Kolvraa, S
[J]. HUMAN MOLECULAR GENETICS, 1998, 7 (04) : 619 - 627
[9] Strong Association of a Common Dihydropyrimidine Dehydrogenase Gene Polymorphism with Fluoropyrimidine-Related Toxicity in Cancer Patients
Gross, Eva
Busse, Birgit
Riemenschneider, Matthias
Neubauer, Steffi
Seck, Katharina
Klein, Hanns-Georg
Kiechle, Marion
Lordick, Florian
Meindl, Alfons
[J]. PLOS ONE, 2008, 3 (12):
[10] Hindorff L., CATALOG PUBLISHED GE

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