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

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Published in Nat Commun on March 23, 2016

Authors

Johannes Kettunen1,2,3,4, Ayşe Demirkan5,6, Peter Würtz1, Harmen H M Draisma7,8,9, Toomas Haller10, Rajesh Rawal11,12, Anika Vaarhorst13, Antti J Kangas1, Leo-Pekka Lyytikäinen14, Matti Pirinen15, René Pool7,8, Antti-Pekka Sarin2,15, Pasi Soininen1,3, Taru Tukiainen16,17, Qin Wang1,3, Mika Tiainen1,3, Tuulia Tynkkynen1,3, Najaf Amin6, Tanja Zeller18,19, Marian Beekman13, Joris Deelen13, Ko Willems van Dijk20,21,22, Tõnu Esko10, Jouke-Jan Hottenga7,8, Elisabeth M van Leeuwen6, Terho Lehtimäki14, Evelin Mihailov10, Richard J Rose23,24, Anton J M de Craen25, Christian Gieger11,12, Mika Kähönen26, Markus Perola2,10,15, Stefan Blankenberg18,19, Markku J Savolainen4,27, Aswin Verhoeven28, Jorma Viikari29, Gonneke Willemsen7,8, Dorret I Boomsma7,8, Cornelia M van Duijn6, Johan Eriksson2,30,31, Antti Jula2, Marjo-Riitta Järvelin4,32,33,34, Jaakko Kaprio35,36,37, Andres Metspalu10, Olli Raitakari38,39, Veikko Salomaa2, P Eline Slagboom13, Melanie Waldenberger11,12, Samuli Ripatti2,15,23,40, Mika Ala-Korpela1,3,4,41,42,43

Author Affiliations

1: Computational Medicine, Faculty of Medicine, University of Oulu, PO Box 5000, 90014 Oulu, Finland.
2: National Institute for Health and Welfare, PO Box 30, FI-00271 Helsinki, Finland.
3: NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, Kuopio 70210, Finland.
4: Biocenter Oulu, University of Oulu, PO Box 5000, FI-90014 Oulu, Finland.
5: Department of Human Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
6: Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
7: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, Room 2B-29, 1081 BT Amsterdam, The Netherlands.
8: EMGO Institute for Health and Care Research, Van der Boechorststraat 7, 1081BT Amsterdam, The Netherlands.
9: Neuroscience Campus Amsterdam, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.
10: Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
11: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
12: Institute of Epidemiology II, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
13: Department of Molecular Epidemiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
14: Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere School of Medicine, Tampere University, Kalevantie 4, Tampere 33014, Finland.
15: Institute for Molecular Medicine (FIMM), University of Helsinki, Biomedicum 2, Tukholmankatu 8, Helsinki 00290, Finland.
16: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.
17: Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 0330, Boston, Massachusetts 02115, USA.
18: German Center for Cardiovascular Research (DZHK e.V.), Partner Site Hamburg/Lübeck/Kiel, Martinistraße 52, 20246 Hamburg, Germany.
19: University Heart Center Hamburg, Clinic of general and interventional Cardiology, Martinistraße 52, 20246 Hamburg, Germany.
20: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
21: Einthoven Laboratory for Experimental Vascular Research, Leiden University Medical Center, Leiden, The Netherlands.
22: Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
23: Department of Public Health, Hjelt Institute, University of Helsinki, PO Box 41 Mannerheimintie 172, Helsinki 00014, Finland.
24: Department of Psychological and Brain Sciences, Indiana University, 1101 E 10th Street, Bloomington, Indiana 47405, USA.
25: Department of Geriatrics and Gerontology, Leiden University Medical Center, Postzone C7-Q, PO Box 9600, 2300RC Leiden, The Netherlands.
26: Department of Clinical Physiology, University of Tampere and Tampere, University Hospital, PO Box 2000, FIN-33521 Tampere, Finland.
27: Medical Research Center, Internal Medicine, Oulu University Hospital, University of Oulu, Aapistie 5A, Oulu FI-90220, Finland.
28: Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
29: Department of Medicine, University of Turku and Turku University Hospital, PB 52, 20521 Turku, Finland.
30: Department of General Practice and Primary Health Care, University of Helsinki, PL 20, Tukholmankatu 8B, Helsinki 00029, Finland.
31: Folkhälsan Research Centre, Helsingfors Universitet, PB 63, Helsinki 00014, Finland.
32: Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London SW7 2AZ, UK.
33: Center for Life Course and Systems Epidemiology, Faculty of Medicine, University of Oulu, PL 5000, 90014 Oulu, Finland.
34: Unit of Primary Care, Oulu University Hospital, P.O. Box 20, OYS, Oulu 90029, Finland.
35: Department of Public Health, University of Helsinki, Helsinki, Finland.
36: National Institute for Health and Welfare, Helsinki, Finland.
37: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
38: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Kiinamyllynkatu 4-8, Turku 20521, Finland.
39: Department of Clinical Physiology, Turku University Hospital, Kiinamyllynkatu 4-8, Turku 20521, Finland.
40: Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
41: Oulu University Hospital, Kajaanintie 50, Oulu 90220, Finland.
42: Computational Medicine, School of Social and Community Medicine, University of Bristol, Senate House, Tyndall Avenue, Bristol, Bristol BS8 1TH, UK.
43: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, Bristol BS8 1TH, UK.

Associated clinical trials:

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS-APO(a)Rx in Patients With High Lipoprotein(a) | NCT02160899

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