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

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, Ursula Schick, Niels Grarup, Zoltán Kutalik, Stella Trompet, Massimo Mangino, Kati Kristiansson, Marian Beekman, Leo-Pekka Lyytikäinen, Joel Eriksson, Peter Henneman, Jari Lahti, Toshiko Tanaka, Jian’an Luan, Fabiola Del Greco M, Dorota Pasko, Frida Renström, Sara M. Willems, Anubha Mahajan, Lynda M. Rose, Xiuqing Guo, Yongmei Liu, Marcus E. Kleber, Louis Pérusse, Tom Gaunt, Tarunveer S. Ahluwalia, Yun Ju Sung, Yolande F. Ramos, Najaf Amin, Antoinette Amuzu, Inês Barroso, Claire Bellis, John Blangero, Brendan M. Buckley, Stefan Böhringer, Yii- Der I Chen, Anton J. N. de Craen, David R. Crosslin, Caroline E. Dale, Zari Dastani, Felix R. Day, Joris Deelen, Graciela E. Delgado, Ayse Demirkan, Francis M. Finucane, Ian Ford, Melissa E. Garcia, Christian Gieger, Stefan Gustafsson, Göran Hallmans, Susan E. Hankinson, Aki S Havulinna, Christian Herder, Dena Hernandez, Andrew A. Hicks, David J. Hunter, Thomas Illig, Erik Ingelsson, Andreea Ioan-Facsinay, John-Olov Jansson, Nancy S. Jenny, Marit E. Jørgensen, Torben Jørgensen, Magnus Karlsson, Wolfgang Koenig, Peter Kraft, Joanneke Kwekkeboom, Tiina Laatikainen, Karl-Heinz Ladwig, Charles A. LeDuc, Gordon Lowe, Yingchang Lu, Pedro Marques-Vidal, Christa Meisinger, Cristina Menni, Andrew P. Morris, Richard H. Myers, Satu Männistö, Mike A. Nalls, Lavinia Paternoster, Annette Peters, Aruna D. Pradhan, Tuomo Rankinen, Laura J. Rasmussen-Torvik, Wolfgang Rathmann, Treva K. Rice, J Brent Richards, Paul M. Ridker, Naveed Sattar, David B. Savage, Stefan Söderberg, Nicholas J. Timpson, Liesbeth Vandenput, Diana van Heemst, Hae-Won Uh, Marie-Claude Vohl, Mark Walker, Heinz-Erich Wichmann, Elisabeth Widén, Andrew R. Wood, Jie Yao, Tanja Zeller, Yiying Zhang, Ingrid Meulenbelt, Margreet Kloppenburg, Arne Astrup, Thorkild I. A. Sørensen, Mark A. Sarzynski, D. C. Rao, Pekka Jousilahti, Erkki Vartiainen, Albert Hofman, Fernando Rivadeneira, André G. Uitterlinden, Eero Kajantie, Clive Osmond, Aarno Palotie, Johan G. Eriksson, Markku Heliövaara, Paul B. Knekt, Seppo Koskinen, Antti Jula, Markus Perola, Risto K. Huupponen, Jorma S. Viikari, Mika Kähönen, Terho Lehtimäki, Olli T. Raitakari, Dan Mellström, Mattias Lorentzon, Juan P. Casas, Stefanie Bandinelli, Winfried März, Aaron Isaacs, Ko W. van Dijk, Cornelia M. van Duijn, Tamara B. Harris, Claude Bouchard, Matthew A. Allison, Daniel I. Chasman, Claes Ohlsson, Lars Lind, Robert A. Scott, Claudia Langenberg, Nicholas J. Wareham, Luigi Ferrucci, Timothy M. Frayling, Peter P. Pramstaller, Ingrid B. Borecki, Dawn M. Waterworth, Sven Bergmann, Gérard Waeber, Peter Vollenweider, Henrik Vestergaard, Torben Hansen, Oluf Pedersen, Frank B. Hu, P Eline Slagboom, Harald Grallert, Tim D. Spector, J.W. Jukema, Robert J. Klein, Erik E Schadt, Paul W. Franks, Cecilia M. Lindgren, Rudolph L. Leibel and Ruth J. F. Loos ()
Additional contact information
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
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
Jennifer Kriebel: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
Mary F Feitosa: Washington University School of Medicine
Åsa K. Hedman: Science for Life Laboratory, Uppsala University
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
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
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
Stella Trompet: Leiden University Medical Center
Massimo Mangino: Department of Twin Research and Genetic Epidemiology King’s College London
Kati Kristiansson: National Institute for Health and Welfare
Marian Beekman: Leiden University Medical Center
Leo-Pekka Lyytikäinen: Fimlab Laboratories
Joel Eriksson: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg
Peter Henneman: Leiden University Medical Center
Jari Lahti: Institute of Behavioural Sciences, University of Helsinki
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
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
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
Yun Ju Sung: 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
Claire Bellis: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore
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
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
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
Stefan Gustafsson: Science for Life Laboratory, 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
Aki S Havulinna: National Institute for Health and Welfare
Christian Herder: German Center for Diabetes Research (DZD)
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
Erik Ingelsson: Science for Life Laboratory, Uppsala University
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
Magnus Karlsson: Clinical and Molecular Osteoporosis Research Unit, Lund University, Skåne University Hospital
Wolfgang Koenig: University of Ulm
Peter Kraft: Harvard T.H. Chan School of Public Health
Joanneke Kwekkeboom: Leiden University Medical Center
Tiina Laatikainen: National Institute for Health and Welfare
Karl-Heinz Ladwig: Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health
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
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
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
Aruna D. Pradhan: Brigham and Women’s Hospital
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
J Brent Richards: Department of Twin Research and Genetic Epidemiology King’s College London
Paul M. Ridker: Brigham and Women’s Hospital
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
Mark Walker: Institute of Cellular Medicine, Newcastle University
Heinz-Erich Wichmann: Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität and Klinikum Grosshadern
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
Yiying Zhang: Division of Molecular Genetics, Department of Pediatrics Columbia University
Ingrid Meulenbelt: Leiden University Medical Center
Margreet Kloppenburg: 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
Mark A. Sarzynski: Human Genomics Laboratory, Pennington Biomedical Research Center
D. C. Rao: 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
André G. Uitterlinden: Erasmus MC
Eero Kajantie: National Institute for Health and Welfare
Clive Osmond: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital
Aarno Palotie: Institute for Molecular Medicine Finland, University of Helsinki
Johan G. Eriksson: National Institute for Health and Welfare
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
Risto K. Huupponen: Drug Development and Therapeutics University of Turku
Jorma S. Viikari: Turku University Hospital
Mika Kähönen: Tampere University Hospital
Terho Lehtimäki: Fimlab Laboratories
Olli T. Raitakari: Turku University Hospital
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
Aaron Isaacs: Genetic Epidemiology Unit, Erasmus MC
Ko W. van Dijk: Leiden University Medical Center
Cornelia M. van Duijn: Genetic Epidemiology Unit, Erasmus MC
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
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
Ingrid B. Borecki: Washington University School of Medicine
Dawn M. Waterworth: GlaxoSmithKline
Sven Bergmann: Swiss Institute of Bioinformatics
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
Torben Hansen: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen
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
Tim D. Spector: Department of Twin Research and Genetic Epidemiology King’s College London
J.W. Jukema: Leiden University Medical Center
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
Cecilia M. Lindgren: Wellcome Trust Centre for Human Genetics, 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

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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

Date: 2016
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DOI: 10.1038/ncomms10494

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