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Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA

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Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. / Kettunen, Johannes; Demirkan, Ayşe; Würtz, Peter; Draisma, Harmen H M; Haller, Toomas; Rawal, Rajesh; Vaarhorst, Anika; Kangas, Antti J; Lyytikäinen, Leo-Pekka; Pirinen, Matti; Pool, René; Sarin, Antti-Pekka; Soininen, Pasi; Tukiainen, Taru; Wang, Qin; Tiainen, Mika; Tynkkynen, Tuulia; Amin, Najaf; Zeller, Tanja; Beekman, Marian; Deelen, Joris; van Dijk, Ko Willems; Esko, Tõnu; Hottenga, Jouke-Jan; van Leeuwen, Elisabeth M; Lehtimäki, Terho; Mihailov, Evelin; Rose, Richard J; de Craen, Anton J M; Gieger, Christian; Kähönen, Mika; Perola, Markus; Blankenberg, Stefan; Savolainen, Markku J; Verhoeven, Aswin; Viikari, Jorma; Willemsen, Gonneke; Boomsma, Dorret I; van Duijn, Cornelia M; Eriksson, Johan; Jula, Antti; Järvelin, Marjo-Riitta; Kaprio, Jaakko; Metspalu, Andres; Raitakari, Olli; Salomaa, Veikko; Slagboom, P Eline; Waldenberger, Melanie; Ripatti, Samuli; Ala-Korpela, Mika.

in: NAT COMMUN, Jahrgang 7, 23.03.2016, S. 11122.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kettunen, J, Demirkan, A, Würtz, P, Draisma, HHM, Haller, T, Rawal, R, Vaarhorst, A, Kangas, AJ, Lyytikäinen, L-P, Pirinen, M, Pool, R, Sarin, A-P, Soininen, P, Tukiainen, T, Wang, Q, Tiainen, M, Tynkkynen, T, Amin, N, Zeller, T, Beekman, M, Deelen, J, van Dijk, KW, Esko, T, Hottenga, J-J, van Leeuwen, EM, Lehtimäki, T, Mihailov, E, Rose, RJ, de Craen, AJM, Gieger, C, Kähönen, M, Perola, M, Blankenberg, S, Savolainen, MJ, Verhoeven, A, Viikari, J, Willemsen, G, Boomsma, DI, van Duijn, CM, Eriksson, J, Jula, A, Järvelin, M-R, Kaprio, J, Metspalu, A, Raitakari, O, Salomaa, V, Slagboom, PE, Waldenberger, M, Ripatti, S & Ala-Korpela, M 2016, 'Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA', NAT COMMUN, Jg. 7, S. 11122. https://doi.org/10.1038/ncomms11122

APA

Kettunen, J., Demirkan, A., Würtz, P., Draisma, H. H. M., Haller, T., Rawal, R., Vaarhorst, A., Kangas, A. J., Lyytikäinen, L-P., Pirinen, M., Pool, R., Sarin, A-P., Soininen, P., Tukiainen, T., Wang, Q., Tiainen, M., Tynkkynen, T., Amin, N., Zeller, T., ... Ala-Korpela, M. (2016). Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. NAT COMMUN, 7, 11122. https://doi.org/10.1038/ncomms11122

Vancouver

Kettunen J, Demirkan A, Würtz P, Draisma HHM, Haller T, Rawal R et al. Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. NAT COMMUN. 2016 Mär 23;7:11122. https://doi.org/10.1038/ncomms11122

Bibtex

@article{4f7c05dce9ca4a269cf908d5f85a2614,
title = "Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA",
abstract = "Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive molecular profiling of circulating metabolites captures highly heritable traits, which can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide association study of genetic influences on 123 circulating metabolic traits quantified by nuclear magnetic resonance metabolomics from up to 24,925 individuals and identify eight novel loci for amino acids, pyruvate and fatty acids. The LPA locus link with cardiovascular risk exemplifies how detailed metabolic profiling may inform underlying aetiology via extensive associations with very-low-density lipoprotein and triglyceride metabolism. Genetic fine mapping and Mendelian randomization uncover wide-spread causal effects of lipoprotein(a) on overall lipoprotein metabolism and we assess potential pleiotropic consequences of genetically elevated lipoprotein(a) on diverse morbidities via electronic health-care records. Our findings strengthen the argument for safe LPA-targeted intervention to reduce cardiovascular risk. ",
keywords = "Adult, Aged, Cardiovascular Diseases/genetics, Chromosome Mapping, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lipoprotein(a)/genetics, Lipoproteins, VLDL/metabolism, Magnetic Resonance Spectroscopy, Male, Mendelian Randomization Analysis, Metabolomics/methods, Middle Aged, Triglycerides/metabolism, Young Adult",
author = "Johannes Kettunen and Ay{\c s}e Demirkan and Peter W{\"u}rtz and Draisma, {Harmen H M} and Toomas Haller and Rajesh Rawal and Anika Vaarhorst and Kangas, {Antti J} and Leo-Pekka Lyytik{\"a}inen and Matti Pirinen and Ren{\'e} Pool and Antti-Pekka Sarin and Pasi Soininen and Taru Tukiainen and Qin Wang and Mika Tiainen and Tuulia Tynkkynen and Najaf Amin and Tanja Zeller and Marian Beekman and Joris Deelen and {van Dijk}, {Ko Willems} and T{\~o}nu Esko and Jouke-Jan Hottenga and {van Leeuwen}, {Elisabeth M} and Terho Lehtim{\"a}ki and Evelin Mihailov and Rose, {Richard J} and {de Craen}, {Anton J M} and Christian Gieger and Mika K{\"a}h{\"o}nen and Markus Perola and Stefan Blankenberg and Savolainen, {Markku J} and Aswin Verhoeven and Jorma Viikari and Gonneke Willemsen and Boomsma, {Dorret I} and {van Duijn}, {Cornelia M} and Johan Eriksson and Antti Jula and Marjo-Riitta J{\"a}rvelin and Jaakko Kaprio and Andres Metspalu and Olli Raitakari and Veikko Salomaa and Slagboom, {P Eline} and Melanie Waldenberger and Samuli Ripatti and Mika Ala-Korpela",
year = "2016",
month = mar,
day = "23",
doi = "10.1038/ncomms11122",
language = "English",
volume = "7",
pages = "11122",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA

AU - Kettunen, Johannes

AU - Demirkan, Ayşe

AU - Würtz, Peter

AU - Draisma, Harmen H M

AU - Haller, Toomas

AU - Rawal, Rajesh

AU - Vaarhorst, Anika

AU - Kangas, Antti J

AU - Lyytikäinen, Leo-Pekka

AU - Pirinen, Matti

AU - Pool, René

AU - Sarin, Antti-Pekka

AU - Soininen, Pasi

AU - Tukiainen, Taru

AU - Wang, Qin

AU - Tiainen, Mika

AU - Tynkkynen, Tuulia

AU - Amin, Najaf

AU - Zeller, Tanja

AU - Beekman, Marian

AU - Deelen, Joris

AU - van Dijk, Ko Willems

AU - Esko, Tõnu

AU - Hottenga, Jouke-Jan

AU - van Leeuwen, Elisabeth M

AU - Lehtimäki, Terho

AU - Mihailov, Evelin

AU - Rose, Richard J

AU - de Craen, Anton J M

AU - Gieger, Christian

AU - Kähönen, Mika

AU - Perola, Markus

AU - Blankenberg, Stefan

AU - Savolainen, Markku J

AU - Verhoeven, Aswin

AU - Viikari, Jorma

AU - Willemsen, Gonneke

AU - Boomsma, Dorret I

AU - van Duijn, Cornelia M

AU - Eriksson, Johan

AU - Jula, Antti

AU - Järvelin, Marjo-Riitta

AU - Kaprio, Jaakko

AU - Metspalu, Andres

AU - Raitakari, Olli

AU - Salomaa, Veikko

AU - Slagboom, P Eline

AU - Waldenberger, Melanie

AU - Ripatti, Samuli

AU - Ala-Korpela, Mika

PY - 2016/3/23

Y1 - 2016/3/23

N2 - Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive molecular profiling of circulating metabolites captures highly heritable traits, which can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide association study of genetic influences on 123 circulating metabolic traits quantified by nuclear magnetic resonance metabolomics from up to 24,925 individuals and identify eight novel loci for amino acids, pyruvate and fatty acids. The LPA locus link with cardiovascular risk exemplifies how detailed metabolic profiling may inform underlying aetiology via extensive associations with very-low-density lipoprotein and triglyceride metabolism. Genetic fine mapping and Mendelian randomization uncover wide-spread causal effects of lipoprotein(a) on overall lipoprotein metabolism and we assess potential pleiotropic consequences of genetically elevated lipoprotein(a) on diverse morbidities via electronic health-care records. Our findings strengthen the argument for safe LPA-targeted intervention to reduce cardiovascular risk.

AB - Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive molecular profiling of circulating metabolites captures highly heritable traits, which can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide association study of genetic influences on 123 circulating metabolic traits quantified by nuclear magnetic resonance metabolomics from up to 24,925 individuals and identify eight novel loci for amino acids, pyruvate and fatty acids. The LPA locus link with cardiovascular risk exemplifies how detailed metabolic profiling may inform underlying aetiology via extensive associations with very-low-density lipoprotein and triglyceride metabolism. Genetic fine mapping and Mendelian randomization uncover wide-spread causal effects of lipoprotein(a) on overall lipoprotein metabolism and we assess potential pleiotropic consequences of genetically elevated lipoprotein(a) on diverse morbidities via electronic health-care records. Our findings strengthen the argument for safe LPA-targeted intervention to reduce cardiovascular risk.

KW - Adult

KW - Aged

KW - Cardiovascular Diseases/genetics

KW - Chromosome Mapping

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Lipoprotein(a)/genetics

KW - Lipoproteins, VLDL/metabolism

KW - Magnetic Resonance Spectroscopy

KW - Male

KW - Mendelian Randomization Analysis

KW - Metabolomics/methods

KW - Middle Aged

KW - Triglycerides/metabolism

KW - Young Adult

U2 - 10.1038/ncomms11122

DO - 10.1038/ncomms11122

M3 - SCORING: Journal article

C2 - 27005778

VL - 7

SP - 11122

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

ER -