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; CARDIoGRAM

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, CARDIoGRAM

Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany. [email protected]

Research output: Contribution to journal › Article › peer-review

847 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
Pages (from-to)	54-60
Number of pages	7
Journal	NATURE
Volume	477
Issue number	7362
DOIs	https://doi.org/10.1038/nature10354
Publication status	Published - 1 Sept 2011

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Biomedical Research
Blood
Child
Chronic Disease
Coronary Artery Disease
Diabetes Mellitus
Drug Industry
Female
Genetic Loci
Genetic Variation
Genome-Wide Association Study
Genotype
Humans
Male
Metabolism
Metabolomics
Middle Aged
Pharmacogenetics
Renal Insufficiency
Risk Factors
Venous Thromboembolism
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nature10354

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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., ... CARDIoGRAM (2011). Human metabolic individuality in biomedical and pharmaceutical research. NATURE, 477(7362), 54-60. https://doi.org/10.1038/nature10354

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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.",

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Suhre, K, Shin, S-Y, Petersen, A-K, 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, H-W, Milburn, MV, Prehn, C, Raffler, J, Ried, JS, Römisch-Margl, W, Samani, NJ, Small, KS, Wichmann, H-E, Zhai, G, Illig, T, Spector, TD, Adamski, J, Soranzo, N, Gieger, C & CARDIoGRAM 2011, 'Human metabolic individuality in biomedical and pharmaceutical research', NATURE, vol. 477, no. 7362, pp. 54-60. https://doi.org/10.1038/nature10354

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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 - Wichmann, H-Erich

AU - Zhai, Guangju

AU - Illig, Thomas

AU - Spector, Tim D

AU - Adamski, Jerzy

AU - Soranzo, Nicole

AU - Gieger, Christian

AU - CARDIoGRAM

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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomedical Research

KW - Blood

KW - Child

KW - Chronic Disease

KW - Coronary Artery Disease

KW - Diabetes Mellitus

KW - Drug Industry

KW - Female

KW - Genetic Loci

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Metabolism

KW - Metabolomics

KW - Middle Aged

KW - Pharmacogenetics

KW - Renal Insufficiency

KW - Risk Factors

KW - Venous Thromboembolism

KW - Young Adult

U2 - 10.1038/nature10354

DO - 10.1038/nature10354

M3 - Article

C2 - 21886157

SN - 1476-4687

VL - 477

SP - 54

EP - 60

JO - NATURE

JF - NATURE

IS - 7362

ER -

Human metabolic individuality in biomedical and pharmaceutical research

Abstract

Keywords

UN SDGs

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