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Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA
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 ncomms11122.pdf | Published version | 459.82 kB | Adobe PDF | View/Open |
| Title: | Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA |
| Authors: | Kettunen, J Demirkan, A Wurtz, P Draisma, HHM Haller, T Rawal, R Vaarhorst, A Kangas, AJ Lyytikaeinen, 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 Lehtimaki, T Mihailov, E Rose, RJ De Craen, AJM Gieger, C Kahonen, M Perola, M Blankenberg, S Savolainen, MJ Verhoeven, A Viikari, J Willemsen, G Boomsma, DI Van Duijn, CM Eriksson, J Jula, A Jarvelin, M-R Kaprio, J Metspalu, A Raitakari, O Salomaa, V Slagboom, PE Waldenberger, M Ripatti, S Ala-Korpela, M |
| Item Type: | Journal Article |
| 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. |
| Issue Date: | 23-Mar-2016 |
| Date of Acceptance: | 24-Feb-2016 |
| URI: | http://hdl.handle.net/10044/1/40193 |
| DOI: | http://dx.doi.org/10.1038/ncomms11122 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Journal / Book Title: | Nature Communications |
| Volume: | 7 |
| Copyright Statement: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics CORONARY-ARTERY-DISEASE EVALUATING ROSUVASTATIN GENETIC-DETERMINANTS INTERVENTION TRIAL JUPITER TRIAL ASSOCIATION LIPOPROTEIN(A) THERAPY RISK JUSTIFICATION Adult Aged Cardiovascular Diseases Chromosome Mapping Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Lipoprotein(a) Lipoproteins, VLDL Magnetic Resonance Spectroscopy Male Mendelian Randomization Analysis Metabolomics Middle Aged Triglycerides Young Adult MD Multidisciplinary |
| Publication Status: | Published |
| Article Number: | 11122 |
| Appears in Collections: | School of Public Health |