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Kettunen, J.* ; Demirkan, A.* ; Würtz, P.* ; Draisma, H.H.M.* ; Haller, T.* ; Rawal, R. ; Vaarhorst, A.A.* ; Kangas, A.J.* ; Lyytikaeinen, L.* ; 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, K.W.* ; Esko, T.* ; Hottenga, J.J.* ; van Leeuwen, E.M.* ; Lehtimäki, T.* ; Mihailov, E.* ; Rose, R.J.* ; de Craen, A.J.M.* ; Gieger, C. ; Kähönen, M.* ; Perola, M.* ; Blankenberg, S.* ; Savolainen, M.J.* ; Verhoeven, A.* ; Viikari, J.* ; Willemsen, G.* ; Boomsma, D.I.* ; van Duijn, C.M.* ; Eriksson, J.* ; Jula, A.* ; Jarvelin, M.R.* ; Kaprio, J.* ; Metspalu, A.* ; Raitakari, O.* ; Salomaa, V.* ; Slagboom, P.E.* ; Waldenberger, M. ; Ripatti, S.* ; Ala-Korpela, M.*

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

Nat. Commun. 7:11122 (2016)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 7, Issue: , Pages: , Article Number: 11122 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology II (EPI2)