title: Metabolomic identification of a novel pathway of blood pressure regulation involving hexadecanedioate.
abstract: High blood pressure is a major contributor to the global burden of disease and discovering novel causal pathways of blood pressure regulation has been challenging. We tested blood pressure associations with 280 fasting blood metabolites in 3980 TwinsUK females. Survival analysis for all-cause mortality was performed on significant independent metabolites (P<8.9×10(-5)). Replication was conducted in 2 independent cohorts KORA (n=1494) and Hertfordshire (n=1515). Three independent animal experiments were performed to establish causality: (1) blood pressure change after increasing circulating metabolite levels in Wistar-Kyoto rats; (2) circulating metabolite change after salt-induced blood pressure elevation in spontaneously hypertensive stroke-prone rats; and (3) mesenteric artery response to noradrenaline and carbachol in metabolite treated and control rats. Of the15 metabolites that showed an independent significant association with blood pressure, only hexadecanedioate, a dicarboxylic acid, showed concordant association with blood pressure (systolic BP: β [95% confidence interval], 1.31 [0.83-1.78], P=6.81×10(-8); diastolic BP: 0.81 [0.5-1.11], P=2.96×10(-7)) and mortality (hazard ratio [95% confidence interval], 1.49 [1.08-2.05]; P=0.02) in TwinsUK. The blood pressure association was replicated in KORA and Hertfordshire. In the animal experiments, we showed that oral hexadecanedioate increased both circulating hexadecanedioate and blood pressure in Wistar-Kyoto rats, whereas blood pressure elevation with oral sodium chloride in hypertensive rats did not affect hexadecanedioate levels. Vascular reactivity to noradrenaline was significantly increased in mesenteric resistance arteries from hexadecanedioate-treated rats compared with controls, indicated by the shift to the left of the concentration-response curve (P=0.013). Relaxation to carbachol did not show any difference. Our findings indicate that hexadecanedioate is causally associated with blood pressure regulation through a novel pathway that merits further investigation.
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Cristina
authors.initials: C
authors.lastname: Menni
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Delyth
authors.initials: D
authors.lastname: Graham
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Nora H J
authors.initials: NH
authors.lastname: Alharbi
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Safaa Md
authors.initials: SM
authors.lastname: Alsanosi
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Martin
authors.initials: M
authors.lastname: McBride
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Philip
authors.initials: P
authors.lastname: Titcombe
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Shin
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Maria
authors.initials: M
authors.lastname: Psatha
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Geisendorfer
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Anja
authors.initials: A
authors.lastname: Huber
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Rui
authors.initials: R
authors.lastname: Wang-Sattler
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Mary Julia
authors.initials: MJ
authors.lastname: Brosnan
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Jeff
authors.initials: J
authors.lastname: Trimmer
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Christian
authors.initials: C
authors.lastname: Reichel
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mohney
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Mark H
authors.initials: MH
authors.lastname: Edwards
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Alistair C
authors.initials: AC
authors.lastname: Church
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Anna F
authors.initials: AF
authors.lastname: Dominiczak
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.). sandosh.padmanabhan@glasgow.ac.uk.
authors.forename: Sandosh
authors.initials: S
authors.lastname: Padmanabhan
authors.affiliation: From the Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom (C.M., M.M., M.P., T.D.S., A.M.V.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., N.H.J.A., S.M.A., M.M.B., A.F.D., S.P.); Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germany (G.K., K.S.); Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.T., M.H.E., C.C.); Wellcome Trust Sanger Institute Human Genetics, Hinxton, United Kingdom (S.-Y.S., N.S.); MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (S.-Y.S.); Chemical Analytics, Seibersdorf Labor GmbH, Seibersdorf, Austria (T.G., A.H., C.R.); Institute of Epidemiology II, Helmholtz Zentrum München, Germany (A.P., C.G.); Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Germany (A.P., R.W.-S., T.X.); Cardiovascular and Metabolic Diseases, Pfizer Worldwide Research and Development, Cambridge, MA (M.J.B.); Edison Pharmaceuticals, Mountain View, CA (J.T.); Metabolon, Inc, Durham, NC (R.P.M.); Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (C.C.); Scottish Pulmonary Vascular Unit, Golden jubilee Hospital, Glasgow, United Kingdom (A.C.C.); Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar (K.S.); and Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom (A.M.V.).
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D003430:Cross-Sectional Studies; D004739:England; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D023421:Models, Animal; D009638:Norepinephrine / Q000494:pharmacology; D010169:Palmitic Acids / Q000378:metabolism*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology; D006113:United Kingdom
chemical_list: D010169:Palmitic Acids; D012965:Sodium Chloride; C012346:hexadecanedioic acid; D002217:Carbachol; D009638:Norepinephrine
keywords: blood pressure; fatty acid synthases; hypertension; metabolomics; mortality