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

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Kettunen , J , Demirkan , A , Wurtz , 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 , Beekman , M , Deelen , J , van Dijk , K W , Esko , T , Hottenga , J-J , van Leeuwen , E M , Lehtimaki , T , Mihailov , E , Rose , R J , de Craen , A J M , Gieger , C , Kahonen , 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 2016 , ' Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA ' , Nature Communications , vol. 7 , 11122 . https://doi.org/10.1038/ncomms11122

Title: Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA
Author: Kettunen, Johannes; Demirkan, Ayse; Wurtz, Peter; Draisma, Harmen H. M.; Haller, Toomas; Rawal, Rajesh; Vaarhorst, Anika; Kangas, Antti J.; Lyytikäinen, Leo-Pekka; Pirinen, Matti; Pool, Rene; 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, Tonu; Hottenga, Jouke-Jan; van Leeuwen, Elisabeth M.; Lehtimaki, Terho; Mihailov, Evelin; Rose, Richard J; de Craen, Anton J. M.; Gieger, Christian; Kahonen, 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; Jarvelin, Marjo-Riitta; Kaprio, Jaakko; Metspalu, Andres; Raitakari, Olli; Salomaa, Veikko; Slagboom, P. Eline; Waldenberger, Melanie; Ripatti, Samuli; Ala-Korpela, Mika
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Harvard University
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
Date: 2016-03
Number of pages: 9
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/161291
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.
Subject: CORONARY-ARTERY-DISEASE
EVALUATING ROSUVASTATIN
GENETIC-DETERMINANTS
INTERVENTION TRIAL
JUPITER TRIAL
ASSOCIATION
LIPOPROTEIN(A)
THERAPY
RISK
JUSTIFICATION
3121 Internal medicine
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