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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

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  • Tuomas O. Kilpeläinen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge
    Genetics of Obesity and Related Metabolic Traits Program, Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai)

  • Jayne F. Martin Carli

    (Columbia University)

  • Alicja A. Skowronski

    (Institute of Human Nutrition, Columbia University)

  • Qi Sun

    (Channing Division of Network Medicine, Department of Medicine Brigham and Women’s Hospital and Harvard Medical School
    Harvard T.H. Chan School of Public Health)

  • Jennifer Kriebel

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
    Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health
    German Center for Diabetes Research (DZD))

  • Mary F Feitosa

    (Washington University School of Medicine)

  • Åsa K. Hedman

    (Science for Life Laboratory, Uppsala University
    Molecular Epidemiology, Uppsala University
    Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Alexander W. Drong

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • James E. Hayes

    (Cell and Developmental Biology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Cornell University
    Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai)

  • Jinghua Zhao

    (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge)

  • Tune H. Pers

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen
    Boston Children’s Hospital
    Broad Institute of the Massachusetts Institute of Technology and Harvard University
    Harvard Medical School)

  • Ursula Schick

    (Genetics of Obesity and Related Metabolic Traits Program, Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai)

  • Niels Grarup

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Zoltán Kutalik

    (Institute of Social and Preventive Medicine, Lausanne University Hospital
    Swiss Institute of Bioinformatics)

  • Stella Trompet

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Massimo Mangino

    (Department of Twin Research and Genetic Epidemiology King’s College London
    National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ Foundation Trust)

  • Kati Kristiansson

    (National Institute for Health and Welfare
    Institute for Molecular Medicine Finland, University of Helsinki)

  • Marian Beekman

    (Leiden University Medical Center)

  • Leo-Pekka Lyytikäinen

    (Fimlab Laboratories
    University of Tampere School of Medicine)

  • Joel Eriksson

    (Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg)

  • Peter Henneman

    (Leiden University Medical Center
    Amsterdam Medical Center)

  • Jari Lahti

    (Institute of Behavioural Sciences, University of Helsinki
    Folkhälsan Research Center)

  • Toshiko Tanaka

    (Translational Gerontology Branch, National Institute on Aging)

  • Jian’an Luan

    (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge)

  • Fabiola Del Greco M

    (Center for Biomedicine, European Academy Bozen/Bolzano (EURAC) - Affiliated Institute of the University of Lübeck)

  • Dorota Pasko

    (Genetics of Complex Traits, University of Exeter Medical School, University of Exeter)

  • Frida Renström

    (Genetic and Molecular Epidemiology Unit, Lund University
    Umeå University)

  • Sara M. Willems

    (Erasmus MC)

  • Anubha Mahajan

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Lynda M. Rose

    (Brigham and Women’s Hospital)

  • Xiuqing Guo

    (LABioMed at Harbor-UCLA Medical Center, Institute for Translational Genomics and Population Sciences)

  • Yongmei Liu

    (Center for Human Genetics)

  • Marcus E. Kleber

    (Medical Faculty Mannheim)

  • Louis Pérusse

    (Laval University, Quebec City, Quebec, Canada G1V 0A6
    Institute of Nutrition and Functional Foods, Quebec City, Quebec, Canada G1V 0A6)

  • Tom Gaunt

    (MRC Integrative Epidemiology Unit and School of Social and Community Medicine, University of Bristol)

  • Tarunveer S. Ahluwalia

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen
    COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Allé
    Steno Diabetes Center)

  • Yun Ju Sung

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Yolande F. Ramos

    (Leiden University Medical Center)

  • Najaf Amin

    (Genetic Epidemiology Unit, Erasmus MC)

  • Antoinette Amuzu

    (Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine)

  • Inês Barroso

    (Wellcome Trust Sanger Institute
    NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital
    The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science)

  • Claire Bellis

    (Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore
    Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology
    Texas Biomedical Research Institute)

  • John Blangero

    (Texas Biomedical Research Institute)

  • Brendan M. Buckley

    (University College Cork)

  • Stefan Böhringer

    (Leiden University Medical Center)

  • Yii-Der I Chen

    (LABioMed at Harbor-UCLA Medical Center, Institute for Translational Genomics and Population Sciences)

  • Anton J. N. de Craen

    (Leiden University Medical Center)

  • David R. Crosslin

    (Division of Medical Genetics, Department of Medicine University of Washington
    University of Washington)

  • Caroline E. Dale

    (Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine)

  • Zari Dastani

    (McGill University)

  • Felix R. Day

    (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge)

  • Joris Deelen

    (Leiden University Medical Center)

  • Graciela E. Delgado

    (Medical Faculty Mannheim)

  • Ayse Demirkan

    (Leiden University Medical Center
    Genetic Epidemiology Unit, Erasmus MC)

  • Francis M. Finucane

    (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge)

  • Ian Ford

    (Robertson Center for Biostatistics, University of Glasgow)

  • Melissa E. Garcia

    (National Heart, Lung, and Blood Institute, NIH)

  • Christian Gieger

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
    Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health
    Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Stefan Gustafsson

    (Science for Life Laboratory, Uppsala University
    Molecular Epidemiology, Uppsala University)

  • Göran Hallmans

    (Umeå University)

  • Susan E. Hankinson

    (Channing Division of Network Medicine, Department of Medicine Brigham and Women’s Hospital and Harvard Medical School
    School of Public Health and Health Sciences, University of Massachusetts
    Harvard T.H. Chan School of Public Health)

  • Aki S Havulinna

    (National Institute for Health and Welfare)

  • Christian Herder

    (German Center for Diabetes Research (DZD)
    Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf)

  • Dena Hernandez

    (Laboratory of Neurogenetics, National Institute on Aging)

  • Andrew A. Hicks

    (Center for Biomedicine, European Academy Bozen/Bolzano (EURAC) - Affiliated Institute of the University of Lübeck)

  • David J. Hunter

    (Harvard T.H. Chan School of Public Health)

  • Thomas Illig

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
    Hannover Unified Biobank, Hannover Medical School
    Institute for Human Genetics, Hannover Medical School)

  • Erik Ingelsson

    (Science for Life Laboratory, Uppsala University
    Molecular Epidemiology, Uppsala University
    Division of Cardiovascular Medicine, Department of Medicine Stanford University School of Medicine)

  • Andreea Ioan-Facsinay

    (Leiden University Medical Center)

  • John-Olov Jansson

    (Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg)

  • Nancy S. Jenny

    (Laboratory for Clinical Biochemistry Research, University of Vermont College of Medicine)

  • Marit E. Jørgensen

    (Steno Diabetes Center)

  • Torben Jørgensen

    (Research Centre for Prevention and Health, Glostrup University Hospital
    Faculty of Medicine, University of Aalborg
    Faculty of Health and Medical Sciences, University of Copenhagen)

  • Magnus Karlsson

    (Clinical and Molecular Osteoporosis Research Unit, Lund University, Skåne University Hospital)

  • Wolfgang Koenig

    (University of Ulm
    Deutsches Herzzentrum München, Technische Universität München
    DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance)

  • Peter Kraft

    (Harvard T.H. Chan School of Public Health)

  • Joanneke Kwekkeboom

    (Leiden University Medical Center)

  • Tiina Laatikainen

    (National Institute for Health and Welfare
    Institute of Public Health and Clinical Nutrition, University of Eastern Finland
    Hospital District of North Karelia)

  • Karl-Heinz Ladwig

    (Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health
    Technische Universität München)

  • Charles A. LeDuc

    (Division of Molecular Genetics, Department of Pediatrics Columbia University)

  • Gordon Lowe

    (Institute of Cardiovascular and Medical Sciences, University of Glasgow)

  • Yingchang Lu

    (Genetics of Obesity and Related Metabolic Traits Program, Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai)

  • Pedro Marques-Vidal

    (Lausanne University Hospital)

  • Christa Meisinger

    (Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health
    German Center for Diabetes Research (DZD))

  • Cristina Menni

    (Department of Twin Research and Genetic Epidemiology King’s College London)

  • Andrew P. Morris

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    University of Liverpool)

  • Richard H. Myers

    (Boston University School of Medicine)

  • Satu Männistö

    (National Institute for Health and Welfare)

  • Mike A. Nalls

    (Laboratory of Neurogenetics, National Institute on Aging)

  • Lavinia Paternoster

    (MRC Integrative Epidemiology Unit and School of Social and Community Medicine, University of Bristol)

  • Annette Peters

    (Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health
    German Center for Diabetes Research (DZD)
    DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance)

  • Aruna D. Pradhan

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Tuomo Rankinen

    (Human Genomics Laboratory, Pennington Biomedical Research Center)

  • Laura J. Rasmussen-Torvik

    (Preventive Medicine, Northwestern Feinberg School of Medicine)

  • Wolfgang Rathmann

    (Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf)

  • Treva K. Rice

    (Washington University School of Medicine
    Washington University School of Medicine)

  • J Brent Richards

    (Department of Twin Research and Genetic Epidemiology King’s College London
    Human Genetics and Epidemiology McGill University)

  • Paul M. Ridker

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Naveed Sattar

    (Faculty of Medicine, BHF Glasgow Cardiovascular Research Centre)

  • David B. Savage

    (The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science)

  • Stefan Söderberg

    (Cardiology and Heart Centre, Umeå University)

  • Nicholas J. Timpson

    (MRC Integrative Epidemiology Unit and School of Social and Community Medicine, University of Bristol)

  • Liesbeth Vandenput

    (Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg)

  • Diana van Heemst

    (Leiden University Medical Center)

  • Hae-Won Uh

    (Leiden University Medical Center)

  • Marie-Claude Vohl

    (Institute of Nutrition and Functional Foods, Quebec City, Quebec, Canada G1V 0A6
    School of Nutrition, Laval University, Quebec City, Quebec, Canada G1V 0A6)

  • Mark Walker

    (Institute of Cellular Medicine, Newcastle University)

  • Heinz-Erich Wichmann

    (Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität and Klinikum Grosshadern
    Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health
    Institute of Medical Statistics and Epidemiology, Technical University Munich)

  • Elisabeth Widén

    (Institute for Molecular Medicine Finland, University of Helsinki)

  • Andrew R. Wood

    (Genetics of Complex Traits, University of Exeter Medical School, University of Exeter)

  • Jie Yao

    (LABioMed at Harbor-UCLA Medical Center, Institute for Translational Genomics and Population Sciences)

  • Tanja Zeller

    (German Center for Cardiovascular Research (DZHK e.V.), partner site Hamburg/Kiel/Lübeck
    Clinic for General and Interventional Cardiology, University Heart Center Hamburg)

  • Yiying Zhang

    (Division of Molecular Genetics, Department of Pediatrics Columbia University)

  • Ingrid Meulenbelt

    (Leiden University Medical Center)

  • Margreet Kloppenburg

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Arne Astrup

    (Faculty of Science, Exercise, and Sports, University of Copenhagen, Copenhagen 1165, Denmark)

  • Thorkild I. A. Sørensen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen
    MRC Integrative Epidemiology Unit and School of Social and Community Medicine, University of Bristol
    Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region)

  • Mark A. Sarzynski

    (Human Genomics Laboratory, Pennington Biomedical Research Center)

  • D. C. Rao

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Pekka Jousilahti

    (National Institute for Health and Welfare)

  • Erkki Vartiainen

    (National Institute for Health and Welfare)

  • Albert Hofman

    (Erasmus MC)

  • Fernando Rivadeneira

    (Erasmus MC
    Erasmus MC)

  • André G. Uitterlinden

    (Erasmus MC
    Erasmus MC)

  • Eero Kajantie

    (National Institute for Health and Welfare
    Children’s Hospital, Helsinki University Central Hospital and University of Helsinki
    MRC Oulu, Oulu University Central Hospital and University of Oulu)

  • Clive Osmond

    (MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital)

  • Aarno Palotie

    (Institute for Molecular Medicine Finland, University of Helsinki
    Wellcome Trust Sanger Institute
    Center for Human Genetic Research, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital)

  • Johan G. Eriksson

    (National Institute for Health and Welfare
    Folkhälsan Research Center
    Department of General Practice and Primary Health Care University of Helsinki)

  • Markku Heliövaara

    (National Institute for Health and Welfare)

  • Paul B. Knekt

    (National Institute for Health and Welfare)

  • Seppo Koskinen

    (National Institute for Health and Welfare)

  • Antti Jula

    (National Institute for Health and Welfare)

  • Markus Perola

    (National Institute for Health and Welfare
    Institute for Molecular Medicine Finland, University of Helsinki
    University of Tartu, Estonian Genome Centre)

  • Risto K. Huupponen

    (Drug Development and Therapeutics University of Turku
    Unit of Clinical Pharmacology, Turku University Hospital)

  • Jorma S. Viikari

    (Turku University Hospital
    University of Turku)

  • Mika Kähönen

    (Tampere University Hospital
    University of Tampere School of Medicine)

  • Terho Lehtimäki

    (Fimlab Laboratories
    University of Tampere School of Medicine)

  • Olli T. Raitakari

    (Turku University Hospital
    Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku)

  • Dan Mellström

    (Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg)

  • Mattias Lorentzon

    (Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg)

  • Juan P. Casas

    (Farr Institute of Health Informatics, University College London)

  • Stefanie Bandinelli

    (Geriatric Unit, Azienda Sanitaria Firenze)

  • Winfried März

    (Medical Faculty Mannheim
    Synlab Academy, Synlab Services LLC
    Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz)

  • Aaron Isaacs

    (Genetic Epidemiology Unit, Erasmus MC)

  • Ko W. van Dijk

    (Leiden University Medical Center)

  • Cornelia M. van Duijn

    (Genetic Epidemiology Unit, Erasmus MC
    Center of Medical Systems Biology)

  • Tamara B. Harris

    (Laboratory of Epidemiology and Population Science, National Institute on Aging)

  • Claude Bouchard

    (Human Genomics Laboratory, Pennington Biomedical Research Center)

  • Matthew A. Allison

    (Family and Preventive Medicine, University of California–San Diego)

  • Daniel I. Chasman

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Claes Ohlsson

    (Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg)

  • Lars Lind

    (Cardiovascular Epidemiology Uppsala University)

  • Robert A. Scott

    (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge)

  • Claudia Langenberg

    (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge)

  • Nicholas J. Wareham

    (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge)

  • Luigi Ferrucci

    (Translational Gerontology Branch, National Institute on Aging)

  • Timothy M. Frayling

    (Genetics of Complex Traits, University of Exeter Medical School, University of Exeter)

  • Peter P. Pramstaller

    (Center for Biomedicine, European Academy Bozen/Bolzano (EURAC) - Affiliated Institute of the University of Lübeck
    General Central Hospital
    University of Lübeck)

  • Ingrid B. Borecki

    (Washington University School of Medicine)

  • Dawn M. Waterworth

    (GlaxoSmithKline)

  • Sven Bergmann

    (Swiss Institute of Bioinformatics
    University of Lausanne)

  • Gérard Waeber

    (Lausanne University Hospital)

  • Peter Vollenweider

    (Lausanne University Hospital)

  • Henrik Vestergaard

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen
    Steno Diabetes Center)

  • Torben Hansen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen
    Faculty of Health Sciences, University of Southern Denmark)

  • Oluf Pedersen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Frank B. Hu

    (Harvard T.H. Chan School of Public Health)

  • P Eline Slagboom

    (Leiden University Medical Center)

  • Harald Grallert

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
    Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health
    German Center for Diabetes Research (DZD))

  • Tim D. Spector

    (Department of Twin Research and Genetic Epidemiology King’s College London)

  • J.W. Jukema

    (Leiden University Medical Center
    Interuniversity Cardiology Institute of the Netherlands
    Durrer Center for Cardiogenetic Research)

  • Robert J. Klein

    (Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai)

  • Erik E Schadt

    (Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai)

  • Paul W. Franks

    (Harvard T.H. Chan School of Public Health
    Genetic and Molecular Epidemiology Unit, Lund University
    Department of Public Health and Clinical Medicine Umeå University)

  • Cecilia M. Lindgren

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Program in Medical and Population Genetics, Broad Institute
    The Big Data Institute, University of Oxford)

  • Rudolph L. Leibel

    (Division of Molecular Genetics, Department of Pediatrics Columbia University)

  • Ruth J. F. Loos

    (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge
    Genetics of Obesity and Related Metabolic Traits Program, Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
    The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai)

Abstract

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P

Suggested Citation

  • Tuomas O. Kilpeläinen & Jayne F. Martin Carli & Alicja A. Skowronski & Qi Sun & Jennifer Kriebel & Mary F Feitosa & Åsa K. Hedman & Alexander W. Drong & James E. Hayes & Jinghua Zhao & Tune H. Pers & , 2016. "Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10494
    DOI: 10.1038/ncomms10494
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