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; Ayse 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; 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

doi:10.1038/ncomms8208

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, Ayse 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 AminHarish 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

^*Corresponding author for this work

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

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 language	English
Pages (from-to)	7208
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8208
Publication status	Published - 12 Jun 2015
Externally published	Yes

Keywords

Blood/metabolism
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide

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10.1038/ncomms8208Licence: CC BY

Cite this

Draisma, H. H. M., Pool, R., Kobl, M., Jansen, R., Petersen, A.-K., Vaarhorst, A. A. M., Yet, I., Haller, T., Demirkan, A., Esko, T., Zhu, G., Böhringer, S., Beekman, M., van Klinken, J. B., Römisch-Margl, W., Prehn, C., Adamski, J., de Craen, A. J. M., van Leeuwen, E. 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

@article{bafa061f80ac4d46a5455fd4a5147b72,

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

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.",

keywords = "Blood/metabolism, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide",

author = "Draisma, {Harmen H M} and Ren{\'e} Pool and Michael Kobl and Rick Jansen and Ann-Kristin Petersen and Vaarhorst, {Anika A M} and Idil Yet and Toomas Haller and Ayse Demirkan and T{\~o}nu Esko and Gu Zhu and Stefan B{\"o}hringer and Marian Beekman and {van Klinken}, {Jan Bert} and Werner R{\"o}misch-Margl and Cornelia Prehn and Jerzy Adamski and {de Craen}, {Anton J M} and {van Leeuwen}, {Elisabeth M} and Najaf Amin and Harish Dharuri and Harm-Jan Westra and Lude Franke and {de Geus}, {Eco J C} and Hottenga, {Jouke Jan} and Gonneke Willemsen and Henders, {Anjali K} and Montgomery, {Grant W} and Nyholt, {Dale R} and Whitfield, {John B} and Penninx, {Brenda W} and Spector, {Tim D} and Andres Metspalu and Slagboom, {P Eline} and {van Dijk}, {Ko Willems} and {'t Hoen}, {Peter A C} and Konstantin Strauch and Martin, {Nicholas G} and {van Ommen}, {Gert-Jan B} and Thomas Illig and Bell, {Jordana T} and Massimo Mangino and Karsten Suhre and McCarthy, {Mark I} and Christian Gieger and Aaron Isaacs and {van Duijn}, {Cornelia M} and Boomsma, {Dorret I}",

year = "2015",

month = jun,

day = "12",

doi = "10.1038/ncomms8208",

language = "English",

volume = "6",

pages = "7208",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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Draisma, HHM, Pool, R, Kobl, M, Jansen, R, Petersen, A-K, 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, H-J, Franke, L, de Geus, EJC, Hottenga, JJ, Willemsen, G, Henders, AK, Montgomery, GW, Nyholt, DR, Whitfield, JB, Penninx, BW, Spector, TD, Metspalu, A, Slagboom, PE, van Dijk, KW, 't Hoen, PAC, Strauch, K, Martin, NG, van Ommen, G-JB, 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, pp. 7208. https://doi.org/10.1038/ncomms8208

TY - JOUR

T1 - Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels

AU - Draisma, Harmen H M

AU - Pool, René

AU - Kobl, Michael

AU - Jansen, Rick

AU - Petersen, Ann-Kristin

AU - Vaarhorst, Anika A M

AU - Yet, Idil

AU - Haller, Toomas

AU - Demirkan, Ayse

AU - Esko, Tõnu

AU - Zhu, Gu

AU - Böhringer, Stefan

AU - Beekman, Marian

AU - van Klinken, Jan Bert

AU - Römisch-Margl, Werner

AU - Prehn, Cornelia

AU - Adamski, Jerzy

AU - de Craen, Anton J M

AU - van Leeuwen, Elisabeth M

AU - Amin, Najaf

AU - Dharuri, Harish

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

AU - Slagboom, P Eline

AU - van Dijk, Ko Willems

AU - 't Hoen, Peter A C

AU - Strauch, Konstantin

AU - Martin, Nicholas G

AU - van Ommen, Gert-Jan B

AU - Illig, Thomas

AU - Bell, Jordana T

AU - Mangino, Massimo

AU - Suhre, Karsten

AU - McCarthy, Mark I

AU - Gieger, Christian

AU - Isaacs, Aaron

AU - van Duijn, Cornelia M

AU - Boomsma, Dorret I

PY - 2015/6/12

Y1 - 2015/6/12

N2 - 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.

AB - 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.

KW - Blood/metabolism

KW - Genome-Wide Association Study

KW - Humans

KW - Polymorphism, Single Nucleotide

U2 - 10.1038/ncomms8208

DO - 10.1038/ncomms8208

M3 - Article

C2 - 26068415

SN - 2041-1723

VL - 6

SP - 7208

JO - Nature Communications

JF - Nature Communications

ER -