Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels

Harmen H.M. Draisma, René Pool, Michael Kobl, Rick Jansen, Ann Kristin Petersen, Anika A.M. Vaarhorst, Idil Yet, Toomas Haller, Ayşe Demirkan, Tõnu Esko, Gu Zhu, Stefan Böhringer, Marian Beekman, Jan Bert Van Klinken, Werner Römisch-Margl, Cornelia Prehn, Jerzy Adamski, Anton J.M. De Craen, Elisabeth M. Van Leeuwen, Najaf Amin & 28 others Harish Dharuri, Harm Jan Westra, Lude Franke, Eco J.C. De Geus, Jouke Jan Hottenga, Gonneke Willemsen, Anjali K. Henders, Grant W. Montgomery, Dale R. Nyholt, John B. Whitfield, Brenda W. Penninx, Tim D. Spector, Andres Metspalu, P. Eline Slagboom, Ko Willems Van Dijk, Peter A.C. 'T Hoen, Konstantin Strauch, Nicholas G. Martin, Gert Jan B. Van Ommen, Thomas Illig, Jordana T. Bell, Massimo Mangino, Karsten Suhre, Mark I. McCarthy, Christian Gieger, Aaron Isaacs, Cornelia M. Van Duijn, Dorret I. Boomsma

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Metabolites are small molecules involved in cellular metabolism, which can be detected in biological samples using metabolomic techniques. Here we present the results of genome-wide association and meta-analyses for variation in the blood serum levels of 129 metabolites as measured by the Biocrates metabolomic platform. In a discovery sample of 7,478 individuals of European descent, we find 4,068 genome- and metabolome-wide significant (Z-test, P<1.09 × 10-9) associations between single-nucleotide polymorphisms (SNPs) and metabolites, involving 59 independent SNPs and 85 metabolites. Five of the fifty-nine independent SNPs are new for serum metabolite levels, and were followed-up for replication in an independent sample (N=1,182). The novel SNPs are located in or near genes encoding metabolite transporter proteins or enzymes (SLC22A16, ARG1, AGPS and ACSL1) that have demonstrated biomedical or pharmaceutical importance. The further characterization of genetic influences on metabolic phenotypes is important for progress in biological and medical research.

Original languageEnglish
Article number7208
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 12 Jun 2015
Externally publishedYes

Fingerprint

genome
metabolites
Genome-Wide Association Study
Metabolites
blood
Single Nucleotide Polymorphism
Blood
Genes
polymorphism
nucleotides
Polymorphism
Metabolomics
Nucleotides
Metabolome
Serum
blood serum
Meta-Analysis
Biomedical Research
transporter
phenotype

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Draisma, H. H. M., Pool, R., Kobl, M., Jansen, R., Petersen, A. K., Vaarhorst, A. A. M., ... Boomsma, D. I. (2015). Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels. Nature Communications, 6, [7208]. https://doi.org/10.1038/ncomms8208

Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels. / Draisma, Harmen H.M.; Pool, René; Kobl, Michael; Jansen, Rick; Petersen, Ann Kristin; Vaarhorst, Anika A.M.; Yet, Idil; Haller, Toomas; Demirkan, Ayşe; Esko, Tõnu; Zhu, Gu; Böhringer, Stefan; Beekman, Marian; Van Klinken, Jan Bert; Römisch-Margl, Werner; Prehn, Cornelia; Adamski, Jerzy; De Craen, Anton J.M.; Van Leeuwen, Elisabeth M.; Amin, Najaf; Dharuri, Harish; Westra, Harm Jan; Franke, Lude; De Geus, Eco J.C.; Hottenga, Jouke Jan; Willemsen, Gonneke; Henders, Anjali K.; Montgomery, Grant W.; Nyholt, Dale R.; Whitfield, John B.; Penninx, Brenda W.; Spector, Tim D.; Metspalu, Andres; Eline Slagboom, P.; Van Dijk, Ko Willems; 'T Hoen, Peter A.C.; Strauch, Konstantin; Martin, Nicholas G.; Van Ommen, Gert Jan B.; Illig, Thomas; Bell, Jordana T.; Mangino, Massimo; Suhre, Karsten; McCarthy, Mark I.; Gieger, Christian; Isaacs, Aaron; Van Duijn, Cornelia M.; Boomsma, Dorret I.

In: Nature Communications, Vol. 6, 7208, 12.06.2015.

Research output: Contribution to journalArticle

Draisma, HHM, Pool, R, Kobl, M, Jansen, R, Petersen, AK, Vaarhorst, AAM, Yet, I, Haller, T, Demirkan, A, Esko, T, Zhu, G, Böhringer, S, Beekman, M, Van Klinken, JB, Römisch-Margl, W, Prehn, C, Adamski, J, De Craen, AJM, Van Leeuwen, EM, Amin, N, Dharuri, H, Westra, HJ, Franke, L, De Geus, EJC, Hottenga, JJ, Willemsen, G, Henders, AK, Montgomery, GW, Nyholt, DR, Whitfield, JB, Penninx, BW, Spector, TD, Metspalu, A, Eline Slagboom, P, Van Dijk, KW, 'T Hoen, PAC, Strauch, K, Martin, NG, Van Ommen, GJB, Illig, T, Bell, JT, Mangino, M, Suhre, K, McCarthy, MI, Gieger, C, Isaacs, A, Van Duijn, CM & Boomsma, DI 2015, 'Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels', Nature Communications, vol. 6, 7208. https://doi.org/10.1038/ncomms8208
Draisma, Harmen H.M. ; Pool, René ; Kobl, Michael ; Jansen, Rick ; Petersen, Ann Kristin ; Vaarhorst, Anika A.M. ; Yet, Idil ; Haller, Toomas ; Demirkan, Ayşe ; Esko, Tõnu ; Zhu, Gu ; Böhringer, Stefan ; Beekman, Marian ; Van Klinken, Jan Bert ; Römisch-Margl, Werner ; Prehn, Cornelia ; Adamski, Jerzy ; De Craen, Anton J.M. ; Van Leeuwen, Elisabeth M. ; Amin, Najaf ; Dharuri, Harish ; Westra, Harm Jan ; Franke, Lude ; De Geus, Eco J.C. ; Hottenga, Jouke Jan ; Willemsen, Gonneke ; Henders, Anjali K. ; Montgomery, Grant W. ; Nyholt, Dale R. ; Whitfield, John B. ; Penninx, Brenda W. ; Spector, Tim D. ; Metspalu, Andres ; Eline Slagboom, P. ; Van Dijk, Ko Willems ; 'T Hoen, Peter A.C. ; Strauch, Konstantin ; Martin, Nicholas G. ; Van Ommen, Gert Jan B. ; Illig, Thomas ; Bell, Jordana T. ; Mangino, Massimo ; Suhre, Karsten ; McCarthy, Mark I. ; Gieger, Christian ; Isaacs, Aaron ; Van Duijn, Cornelia M. ; Boomsma, Dorret I. / Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels. In: Nature Communications. 2015 ; Vol. 6.
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AU - Petersen, Ann Kristin

AU - Vaarhorst, Anika A.M.

AU - Yet, Idil

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AU - Amin, Najaf

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AU - Westra, Harm Jan

AU - Franke, Lude

AU - De Geus, Eco J.C.

AU - Hottenga, Jouke Jan

AU - Willemsen, Gonneke

AU - Henders, Anjali K.

AU - Montgomery, Grant W.

AU - Nyholt, Dale R.

AU - Whitfield, John B.

AU - Penninx, Brenda W.

AU - Spector, Tim D.

AU - Metspalu, Andres

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AU - Isaacs, Aaron

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