Human metabolic individuality in biomedical and pharmaceutical research

Karsten Suhre; So Youn Shin; Ann Kristin Petersen; Robert P. Mohney; David Meredith; Brigitte Wägele; Elisabeth Altmaier; Panos Deloukas; Jeanette Erdmann; Elin Grundberg; Christopher J. Hammond; Martin Hrabé De Angelis; Gabi Kastenmüller; Anna Köttgen; Florian Kronenberg; Massimo Mangino; Christa Meisinger; Thomas Meitinger; Hans Werner Mewes; Michael V. Milburn; Cornelia Prehn; Johannes Raffler; Janina S. Ried; Werner Römisch-Margl; Nilesh J. Samani; Kerrin S. Small; H. -Erich Wichmann; Guangju Zhai; Thomas Illig; Tim D. Spector; Jerzy Adamski; Nicole Soranzo; Christian Gieger

doi:10.1038/nature10354

Human metabolic individuality in biomedical and pharmaceutical research

Karsten Suhre^*, So Youn Shin, Ann Kristin Petersen, Robert P. Mohney, David Meredith, Brigitte Wägele, Elisabeth Altmaier, Panos Deloukas, Jeanette Erdmann, Elin Grundberg, Christopher J. Hammond, Martin Hrabé De Angelis, Gabi Kastenmüller, Anna Köttgen, Florian Kronenberg, Massimo Mangino, Christa Meisinger, Thomas Meitinger, Hans Werner Mewes, Michael V. MilburnCornelia Prehn, Johannes Raffler, Janina S. Ried, Werner Römisch-Margl, Nilesh J. Samani, Kerrin S. Small, H. -Erich Wichmann, Guangju Zhai, Thomas Illig, Tim D. Spector, Jerzy Adamski, Nicole Soranzo, Christian Gieger

^*Corresponding author for this work

Clinic of Internal Medicine II - Cardiology

489 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Nature
Volume	477
Issue number	7362
Pages (from-to)	54-62
Number of pages	9
ISSN	0028-0836
DOIs	https://doi.org/10.1038/nature10354
Publication status	Published - 01.09.2011

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Suhre, K., Shin, S. Y., Petersen, A. K., Mohney, R. P., Meredith, D., Wägele, B., Altmaier, E., Deloukas, P., Erdmann, J., Grundberg, E., Hammond, C. J., De Angelis, M. H., Kastenmüller, G., Köttgen, A., Kronenberg, F., Mangino, M., Meisinger, C., Meitinger, T., Mewes, H. W., ... Gieger, C. (2011). Human metabolic individuality in biomedical and pharmaceutical research. Nature, 477(7362), 54-62. https://doi.org/10.1038/nature10354

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title = "Human metabolic individuality in biomedical and pharmaceutical research",

abstract = "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.",

author = "Karsten Suhre and Shin, {So Youn} and Petersen, {Ann Kristin} and Mohney, {Robert P.} and David Meredith and Brigitte W{\"a}gele and Elisabeth Altmaier and Panos Deloukas and Jeanette Erdmann and Elin Grundberg and Hammond, {Christopher J.} and {De Angelis}, {Martin Hrab{\'e}} and Gabi Kastenm{\"u}ller and Anna K{\"o}ttgen and Florian Kronenberg and Massimo Mangino and Christa Meisinger and Thomas Meitinger and Mewes, {Hans Werner} and Milburn, {Michael V.} and Cornelia Prehn and Johannes Raffler and Ried, {Janina S.} and Werner R{\"o}misch-Margl and Samani, {Nilesh J.} and Small, {Kerrin S.} and {-Erich Wichmann}, H. and Guangju Zhai and Thomas Illig and Spector, {Tim D.} and Jerzy Adamski and Nicole Soranzo and Christian Gieger",

year = "2011",

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doi = "10.1038/nature10354",

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Suhre, K, Shin, SY, Petersen, AK, Mohney, RP, Meredith, D, Wägele, B, Altmaier, E, Deloukas, P, Erdmann, J, Grundberg, E, Hammond, CJ, De Angelis, MH, Kastenmüller, G, Köttgen, A, Kronenberg, F, Mangino, M, Meisinger, C, Meitinger, T, Mewes, HW, Milburn, MV, Prehn, C, Raffler, J, Ried, JS, Römisch-Margl, W, Samani, NJ, Small, KS, -Erich Wichmann, H, Zhai, G, Illig, T, Spector, TD, Adamski, J, Soranzo, N & Gieger, C 2011, 'Human metabolic individuality in biomedical and pharmaceutical research', Nature, vol. 477, no. 7362, pp. 54-62. https://doi.org/10.1038/nature10354

TY - JOUR

T1 - Human metabolic individuality in biomedical and pharmaceutical research

AU - Suhre, Karsten

AU - Shin, So Youn

AU - Petersen, Ann Kristin

AU - Mohney, Robert P.

AU - Meredith, David

AU - Wägele, Brigitte

AU - Altmaier, Elisabeth

AU - Deloukas, Panos

AU - Erdmann, Jeanette

AU - Grundberg, Elin

AU - Hammond, Christopher J.

AU - De Angelis, Martin Hrabé

AU - Kastenmüller, Gabi

AU - Köttgen, Anna

AU - Kronenberg, Florian

AU - Mangino, Massimo

AU - Meisinger, Christa

AU - Meitinger, Thomas

AU - Mewes, Hans Werner

AU - Milburn, Michael V.

AU - Prehn, Cornelia

AU - Raffler, Johannes

AU - Ried, Janina S.

AU - Römisch-Margl, Werner

AU - Samani, Nilesh J.

AU - Small, Kerrin S.

AU - -Erich Wichmann, H.

AU - Zhai, Guangju

AU - Illig, Thomas

AU - Spector, Tim D.

AU - Adamski, Jerzy

AU - Soranzo, Nicole

AU - Gieger, Christian

PY - 2011/9/1

Y1 - 2011/9/1

N2 - 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.

AB - 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.

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U2 - 10.1038/nature10354

DO - 10.1038/nature10354

M3 - Journal articles

C2 - 21886157

AN - SCOPUS:80052398214

SN - 0028-0836

VL - 477

SP - 54

EP - 62

JO - Nature

JF - Nature

IS - 7362

ER -

Human metabolic individuality in biomedical and pharmaceutical research

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