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

Authors :
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
Source :
Kettunen, J., A. Demirkan, P. Würtz, H. H. Draisma, T. Haller, R. Rawal, A. Vaarhorst, et al. 2016. “Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA.” Nature Communications 7 (1): 11122. doi:10.1038/ncomms11122. http://dx.doi.org/10.1038/ncomms11122.
Publication Year :
2016
Publisher :
Nature Publishing Group, 2016.

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.

Details

Language :
English
ISSN :
20411723
Database :
Digital Access to Scholarship at Harvard (DASH)
Journal :
Kettunen, J., A. Demirkan, P. Würtz, H. H. Draisma, T. Haller, R. Rawal, A. Vaarhorst, et al. 2016. “Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA.” Nature Communications 7 (1): 11122. doi:10.1038/ncomms11122. http://dx.doi.org/10.1038/ncomms11122.
Publication Type :
Academic Journal
Accession number :
edshld.1.29407767
Document Type :
Journal Article
Full Text :
https://doi.org/10.1038/ncomms11122