Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Cohort Studies Gene Expression Regulation Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study HLA-DRB1 Chains / genetics Humans Interleukin 1 Receptor Antagonist Protein / genetics Interleukin-1 / genetics Interleukin-6 / blood Polymorphism, Single Nucleotide Receptors, Interleukin-6 / genetics White People / genetics

Journal

Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958

Informations de publication

Date de publication:
27 04 2021
Historique:
received: 02 12 2020
revised: 02 12 2020
accepted: 04 01 2021
pubmed: 1 2 2021
medline: 26 11 2021
entrez: 31 1 2021
Statut: ppublish

Résumé

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Identifiants

DOI: 10.1093/hmg/ddab023 PMID: 33517400 PMC: PMC8098112
pubmed: 33517400
pii: 6124523
doi: 10.1093/hmg/ddab023
pmc: PMC8098112
doi:

Substances chimiques

HLA-DRB1 Chains 0
IL1F10 protein, human 0
IL1RN protein, human 0
IL6R protein, human 0
Interleukin 1 Receptor Antagonist Protein 0
Interleukin-1 0
Interleukin-6 0
Receptors, Interleukin-6 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

393-409

Subventions

Organisme : Medical Research Council
ID : MC_UU_00011/4
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/19/4/34452
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : U01 HL120393
Pays : United States
Organisme : Medical Research Council
ID : G0700704
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/6
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R024227/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1001401
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/4
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202802/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K026992/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/16/11/32334
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : British Heart Foundation
ID : SP/13/6/30554
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S011676/1
Pays : United Kingdom

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press.

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Auteurs

Tarunveer S Ahluwalia (TS)

Steno Diabetes Center Copenhagen, Gentofte DK2820, Denmark.
Department of Biology, The Bioinformatics Center, University of Copenhagen, Copenhagen DK2200, Denmark.
ORCID: 0000-0002-7464-3354

Bram P Prins (BP)

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.

Mohammadreza Abdollahi (M)

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.

Nicola J Armstrong (NJ)

Mathematics and Statistics, Murdoch University, Perth 6150, Australia.

Stella Aslibekyan (S)

Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, Alabama 35233, USA.

Lisa Bain (L)

QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.

Barbara Jefferis (B)

Department of Primary Care & Population Health, UCL Institute of Epidemiology & Health Care, University College London, London NW3 2PF, UK.

Jens Baumert (J)

Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.

Marian Beekman (M)

Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.

Yoav Ben-Shlomo (Y)

Population Health Sciences, University of Bristol, Bristol BS8 2PS, UK.

Joshua C Bis (JC)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.

Braxton D Mitchell (BD)

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21202, USA.

Eco de Geus (E)

Department of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.
Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam 1105 AZ, The Netherlands.

Graciela E Delgado (GE)

Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim 68167, Germany.

Diana Marek (D)

SIB Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.

Joel Eriksson (J)

Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, Centre for Bone and Arthritis Research (CBAR), University of Gothenburg, Gothenburg 41345, Sweden.

Eero Kajantie (E)

Chronic Disease Prevention Unit, National Institute for Health and Welfare, PO Box 30, Helsinki 00271, Finland.
Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Helsinki 00014, Finland.

Stavroula Kanoni (S)

William Harvey Research Institute, Barts & the London Medical School, Queen Mary University of London, London EC1M 6BQ, UK.

John P Kemp (JP)

The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia.
MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.

Chen Lu (C)

Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.

Riccardo E Marioni (RE)

Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK.

Stela McLachlan (S)

Usher Institute, University of Edinburgh, Edinburgh EH8 9AG, UK.

Yuri Milaneschi (Y)

Department of Psychiatry, Amsterdam UMC, Vrije Universiteit, Amsterdam 1081 HJ, The Netherlands.

Ilja M Nolte (IM)

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.

Alexandros M Petrelis (AM)

Université de Lorraine, Inserm, IGE-PCV, Nancy 54000, France.

Eleonora Porcu (E)

Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato (CA) 09042, Italy.

Maria Sabater-Lleal (M)

Cardiovascular Medicine, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
Unit of Genomics of Complex Diseases, Institut d'Investigació Biomèdica Sant Pau (IIB-Sant Pau), Barcelona 08041, Spain.

Elnaz Naderi (E)

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.

Ilkka Seppälä (I)

Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland.

Tina Shah (T)

Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.

Gaurav Singhal (G)

Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia.

Marie Standl (M)

Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.

Alexander Teumer (A)

Institute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
ORCID: 0000-0002-8309-094X

Anbupalam Thalamuthu (A)

Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia.

Elisabeth Thiering (E)

Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
Division of Metabolic Diseases and Nutritional Medicine, Ludwig-Maximilians-University of Munich, Dr. von Hauner Children's Hospital, Munich 80337, Germany.

Stella Trompet (S)

Department of Cardiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.

Christie M Ballantyne (CM)

Baylor College of Medicine, Houston, TX 77030, USA.

Emelia J Benjamin (EJ)

National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA.
Section of Cardiovascular Medicine and Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

Juan P Casas (JP)

Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.

Catherine Toben (C)

Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia.

George Dedoussis (G)

44Department of Nutrition-Dietetics, Harokopio University, Athens 17671, Greece.

Joris Deelen (J)

Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.

Peter Durda (P)

Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA.

Jorgen Engmann (J)

Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.

Mary F Feitosa (MF)

Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.

Harald Grallert (H)

Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
German Center for Diabetes Research (DZD), Neuherberg 85764, Germany.

Ann Hammarstedt (A)

The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg SE-41345, Sweden.

Sarah E Harris (SE)

Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.

Georg Homuth (G)

Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17475, Germany.

Jouke-Jan Hottenga (JJ)

Department of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.
Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam 1105 AZ, The Netherlands.

Sirpa Jalkanen (S)

MediCity Research Laboratory, University of Turku, Turku 20520, Finland.
Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland.

Yalda Jamshidi (Y)

Genetics Research Centre, Molecular and Clinical Sciences Institute, St George's University of London, London SW17 0RE, UK.

Magdalene C Jawahar (MC)

Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia.

Tine Jess (T)

55Department of Epidemiology Research, Statens Serum Institute, Copenhagen DK2300, Denmark.

Mika Kivimaki (M)

Department of Epidemiology & Public Health, UCL Institute of Epidemiology & Health Care, University College London, London WC1E 7HB, UK.

Marcus E Kleber (ME)

Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim 68167, Germany.

Jari Lahti (J)

Turku Institute for Advanced Studies, University of Turku, Turku 20014, Finland.
Department of Psychology and Logopedics, University of Helsinki, Helsinki 00014, Finland.

Yongmei Liu (Y)

Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.

Pedro Marques-Vidal (P)

Department of Internal Medicine, Lausanne University Hospital (CHUV), Lausanne 1011, Switzerland.
University of Lausanne, Lausanne 1011, Switzerland.

Dan Mellström (D)

Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, Centre for Bone and Arthritis Research (CBAR), University of Gothenburg, Gothenburg 41345, Sweden.

Simon P Mooijaart (SP)

Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.

Martina Müller-Nurasyid (M)

IBE, Faculty of Medicine, Ludwig Maximilians University (LMU) Munich, Munich 81377, Germany.
Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johhanes Gutenberg University, Mainz 55101, Germany.
ORCID: 0000-0003-3793-5910

Brenda Penninx (B)

Department of Psychiatry, Amsterdam UMC, Vrije Universiteit, Amsterdam 1081 HJ, The Netherlands.

Joana A Revez (JA)

QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
ORCID: 0000-0003-3204-5396

Peter Rossing (P)

Steno Diabetes Center Copenhagen, Gentofte DK2820, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen DK2200, Denmark.

Katri Räikkönen (K)

Department of Psychology and Logopedics, University of Helsinki, Helsinki 00014, Finland.

Naveed Sattar (N)

BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow G12 8TA, UK.

Hubert Scharnagl (H)

66Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria.

Bengt Sennblad (B)

Cardiovascular Medicine, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala 75124, Sweden.

Angela Silveira (A)

Cardiovascular Medicine, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden.

Beate St Pourcain (BS)

MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.
Max Planck Institute for Psycholinguistics, Nijmegen XD 6525, The Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6525 AJ, The Netherlands.

Nicholas J Timpson (NJ)

MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.

Julian Trollor (J)

Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia.
Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney 2031, Australia.

Jenny van Dongen (J)

Department of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.
Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam 1105 AZ, The Netherlands.

Diana Van Heemst (D)

Baylor College of Medicine, Houston, TX 77030, USA.

Sophie Visvikis-Siest (S)

Université de Lorraine, Inserm, IGE-PCV, Nancy 54000, France.

Peter Vollenweider (P)

Department of Internal Medicine, Lausanne University Hospital (CHUV), Lausanne 1011, Switzerland.
University of Lausanne, Lausanne 1011, Switzerland.

Uwe Völker (U)

MediCity Research Laboratory, University of Turku, Turku 20520, Finland.

Melanie Waldenberger (M)

Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.

Gonneke Willemsen (G)

Department of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.
Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam 1105 AZ, The Netherlands.

Delilah Zabaneh (D)

Department of Genetics, Environment and Evolution, University College London Genetics Institute, London WC1E 6BT, UK.

Richard W Morris (RW)

Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1UD, UK.

Donna K Arnett (DK)

Dean's Office, College of Public Health, University of Kentucky, Lexington, KY 40536, USA.

Bernhard T Baune (BT)

Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Parkville 3000, Australia.
Department of Psychiatry and Psychotherapy, University of Muenster, Muenster 48149, Germany.
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3000, Australia.

Dorret I Boomsma (DI)

Department of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam 1081 BT, The Netherlands.
Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam 1105 AZ, The Netherlands.

Yen-Pei C Chang (YC)

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21202, USA.

Ian J Deary (IJ)

Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.

Panos Deloukas (P)

William Harvey Research Institute, Barts & the London Medical School, Queen Mary University of London, London EC1M 6BQ, UK.
77Centre for Genomic Health, Queen Mary University of London, London EC1M 6BQ, UK.

Johan G Eriksson (JG)

National Institute for Health and Welfare, University of Helsinki, Helsinki 00014, Finland.
Department of General Practice and Primary Health Care, University of Helsinki, Helsinki 00014, Finland.

David M Evans (DM)

The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia.
MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.

Manuel A Ferreira (MA)

QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.

Tom Gaunt (T)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol BS6 2BN, UK.
Population Health Science, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK.

Vilmundur Gudnason (V)

Icelandic Heart Association, Kópavogur 201, Iceland.
Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.

Anders Hamsten (A)

Cardiovascular Medicine, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden.

Joachim Heinrich (J)

Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.
Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Munich 81377, Germany.
Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne 3010, Australia.

Aroon Hingorani (A)

Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.

Steve E Humphries (SE)

Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.

J Wouter Jukema (JW)

Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.
Durrer Center for Cardiogenetic Research, Amsterdam 1105 AZ, The Netherlands.

Wolfgang Koenig (W)

Deutsches Herzzentrum München, Technische Universität München, Munich 80636, Germany.
88DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich 80336, Germany.
Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm 89081, Germany.

Meena Kumari (M)

Department of Epidemiology & Public Health, UCL Institute of Epidemiology & Health Care, University College London, London WC1E 7HB, UK.
Institute for Social and Economic Research, University of Essex, Colchester CO4 3SQ, Germany.

Zoltan Kutalik (Z)

SIB Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
University Center for Primary Care and Public Health, University of Lausanne, Lausanne 1010, Switzerland.

Deborah A Lawlor (DA)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol BS6 2BN, UK.
Population Health Science, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK.

Terho Lehtimäki (T)

Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland.

Winfried März (W)

Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim 68167, Germany.
66Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria.
SYNLAB Academy, SYNALB Holding Deutschland GmbH, Mannheim 68163, Germany.

Karen A Mather (KA)

Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia.
Neuroscience Research Australia, Sydney 2031, Australia.

Silvia Naitza (S)

Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato (CA) 09042, Italy.

Matthias Nauck (M)

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald 17475, Germany.

Claes Ohlsson (C)

Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, Centre for Bone and Arthritis Research (CBAR), University of Gothenburg, Gothenburg 41345, Sweden.

Jackie F Price (JF)

Usher Institute, University of Edinburgh, Edinburgh EH8 9AG, UK.

Olli Raitakari (O)

Centre for Population Health Research, University of Turku, Turku University Hospital, Turku 20520, Finland.
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland.
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20014, Finland.

Ken Rice (K)

Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.

Perminder S Sachdev (PS)

Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia.
Neuropsychiatric Institute, Prince of Wales Hospital, Sydney 2031, Australia.

Eline Slagboom (E)

Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.

Thorkild I A Sørensen (TIA)

Novo Nordisk Foundation Center For Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK2200, Denmark.
Department of Public Health, Section on Epidemiology, University of Copenhagen, Copenhagen DK1014, Denmark.

Tim Spector (T)

Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.

David Stacey (D)

MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.

Maria G Stathopoulou (MG)

Université de Lorraine, Inserm, IGE-PCV, Nancy 54000, France.

Toshiko Tanaka (T)

Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA.

S Goya Wannamethee (SG)

Department of Primary Care & Population Health, UCL Institute of Epidemiology & Health Care, University College London, London NW3 2PF, UK.

Peter Whincup (P)

Population Health Research Institute, St George's, University of London, London SW17 0RE, UK.

Jerome I Rotter (JI)

Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

Abbas Dehghan (A)

Department of Epidemiology, Erasmus MC, Rotterdam 3000 CA, The Netherlands.

Eric Boerwinkle (E)

Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

Bruce M Psaty (BM)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
Departments of Epidemiology and Health Services, University of Washington, Seattle, WA 98101, USA.

Harold Snieder (H)

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.

Behrooz Z Alizadeh (BZ)

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.

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