A genome-wide perspective of genetic variation in human metabolism

Thomas Illig; Christian Gieger; Guangju Zhai; Werner Roemisch-Margl; Rui Wang-Sattler; Cornelia Prehn; Elisabeth Altmaier; Gabi Kastenmueller; Bernet S. Kato; Hans-Werner Mewes; Thomas Meitinger; Martin Hrabe de Angelis; Florian Kronenberg; Nicole Soranzo; H-Erich Wichmann; Tim D. Spector; Jerzy Adamski; Karsten Suhre

doi:10.1038/ng.507

A genome-wide perspective of genetic variation in human metabolism

Thomas Illig, Christian Gieger, Guangju Zhai, Werner Roemisch-Margl, Rui Wang-Sattler, Cornelia Prehn, Elisabeth Altmaier, Gabi Kastenmueller, Bernet S. Kato, Hans-Werner Mewes, Thomas Meitinger, Martin Hrabe de Angelis, Florian Kronenberg, Nicole Soranzo, H-Erich Wichmann, Tim D. Spector, Jerzy Adamski, Karsten Suhre

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Abstract

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.

Original language	English
Pages (from-to)	137 - U66
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	2
DOIs	https://doi.org/10.1038/ng.507
Publication status	Published - Feb 2010

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Illig, T., Gieger, C., Zhai, G., Roemisch-Margl, W., Wang-Sattler, R., Prehn, C., Altmaier, E., Kastenmueller, G., Kato, B. S., Mewes, H.-W., Meitinger, T., de Angelis, M. H., Kronenberg, F., Soranzo, N., Wichmann, H.-E., Spector, T. D., Adamski, J., & Suhre, K. (2010). A genome-wide perspective of genetic variation in human metabolism. Nature Genetics, 42(2), 137 - U66. https://doi.org/10.1038/ng.507

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title = "A genome-wide perspective of genetic variation in human metabolism",

abstract = "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.",

author = "Thomas Illig and Christian Gieger and Guangju Zhai and Werner Roemisch-Margl and Rui Wang-Sattler and Cornelia Prehn and Elisabeth Altmaier and Gabi Kastenmueller and Kato, {Bernet S.} and Hans-Werner Mewes and Thomas Meitinger and {de Angelis}, {Martin Hrabe} and Florian Kronenberg and Nicole Soranzo and H-Erich Wichmann and Spector, {Tim D.} and Jerzy Adamski and Karsten Suhre",

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doi = "10.1038/ng.507",

language = "English",

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Illig, T, Gieger, C, Zhai, G, Roemisch-Margl, W, Wang-Sattler, R, Prehn, C, Altmaier, E, Kastenmueller, G, Kato, BS, Mewes, H-W, Meitinger, T, de Angelis, MH, Kronenberg, F, Soranzo, N, Wichmann, H-E, Spector, TD, Adamski, J & Suhre, K 2010, 'A genome-wide perspective of genetic variation in human metabolism', Nature Genetics, vol. 42, no. 2, pp. 137 - U66. https://doi.org/10.1038/ng.507

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T1 - A genome-wide perspective of genetic variation in human metabolism

AU - Illig, Thomas

AU - Gieger, Christian

AU - Zhai, Guangju

AU - Roemisch-Margl, Werner

AU - Wang-Sattler, Rui

AU - Prehn, Cornelia

AU - Altmaier, Elisabeth

AU - Kastenmueller, Gabi

AU - Kato, Bernet S.

AU - Mewes, Hans-Werner

AU - Meitinger, Thomas

AU - de Angelis, Martin Hrabe

AU - Kronenberg, Florian

AU - Soranzo, Nicole

AU - Wichmann, H-Erich

AU - Spector, Tim D.

AU - Adamski, Jerzy

AU - Suhre, Karsten

PY - 2010/2

Y1 - 2010/2

N2 - 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.

AB - 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.

U2 - 10.1038/ng.507

DO - 10.1038/ng.507

M3 - Article

SN - 1546-1718

VL - 42

SP - 137 - U66

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

A genome-wide perspective of genetic variation in human metabolism

Abstract

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