A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone–Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulation

• Andrea D. Coviello ,

  Contributed equally to this work with: Andrea D. Coviello, Robin Haring, Melissa Wellons, Dhananjay Vaidya, Terho Lehtimäki, Sarah Keildson

  Affiliations Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, United States of America, Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, Massachusetts, United States of America, National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, United States of America

  ⨯
• Robin Haring ,

  Contributed equally to this work with: Andrea D. Coviello, Robin Haring, Melissa Wellons, Dhananjay Vaidya, Terho Lehtimäki, Sarah Keildson

  Affiliation Institute for Clinical Chemistry and Laboratory Medicine, University Medicine, Ernst-Moritz-Arndt University of Greifswald, Greifswald, Germany

  ⨯
• Melissa Wellons ,

  Contributed equally to this work with: Andrea D. Coviello, Robin Haring, Melissa Wellons, Dhananjay Vaidya, Terho Lehtimäki, Sarah Keildson

  Affiliation Department of Medicine and Department of Obstetrics and Gynecology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America

  ⨯
• Dhananjay Vaidya ,

  Contributed equally to this work with: Andrea D. Coviello, Robin Haring, Melissa Wellons, Dhananjay Vaidya, Terho Lehtimäki, Sarah Keildson

  Affiliation Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America

  ⨯
• Terho Lehtimäki ,

  Contributed equally to this work with: Andrea D. Coviello, Robin Haring, Melissa Wellons, Dhananjay Vaidya, Terho Lehtimäki, Sarah Keildson

  Affiliation Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital and University of Tampere School of Medicine, Tampere, Finland

  ⨯
• Sarah Keildson ,

  Contributed equally to this work with: Andrea D. Coviello, Robin Haring, Melissa Wellons, Dhananjay Vaidya, Terho Lehtimäki, Sarah Keildson

  Affiliation Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

  ⨯
• Kathryn L. Lunetta,

  Affiliation Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America

  ⨯
• Chunyan He,

  Affiliations Department of Public Health, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, United States of America

  ⨯
• Myriam Fornage,

  Affiliation University of Texas Health Sciences Center at Houston, Houston, Texas, United States of America

  ⨯
• Vasiliki Lagou,

  Affiliations Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom

  ⨯
• Massimo Mangino,

  Affiliation Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom

  ⨯
• N. Charlotte Onland-Moret,

  Affiliation Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

  ⨯
• Brian Chen,

  Affiliation Program on Genomics and Nutrition and the Center for Metabolic Disease Prevention, School of Public Health, University of California Los Angeles, Los Angeles, California, United States of America

  ⨯
• Joel Eriksson,

  Affiliation Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

  ⨯
• Melissa Garcia,

  Affiliation Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, United States of America

  ⨯
• Yong Mei Liu,

  Affiliations Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America, Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States of America

  ⨯
• Annemarie Koster,

  Affiliation Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, United States of America

  ⨯
• Kurt Lohman,

  Affiliation Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America

  ⨯
• Leo-Pekka Lyytikäinen,

  Affiliation Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital and University of Tampere School of Medicine, Tampere, Finland

  ⨯
• Ann-Kristin Petersen,

  Affiliation Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany

  ⨯
• Jennifer Prescott,

  Affiliations Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America

  ⨯
• Lisette Stolk,

  Affiliations Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, Netherlands Consortium of Healthy Aging, Rotterdam, The Netherlands

  ⨯
• Liesbeth Vandenput,

  Affiliation Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

  ⨯
• Andrew R. Wood,

  Affiliation Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom

  ⨯
• Wei Vivian Zhuang,

  Affiliation Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America

  ⨯
• Aimo Ruokonen,

  Affiliation Institute of Diagnostics, University of Oulu, Oulu, Finland

  ⨯
• Anna-Liisa Hartikainen,

  Affiliation Department of Obstetrics and Gynecology, University Hospital of Oulu, Oulu, Finland

  ⨯
• Anneli Pouta,

  Affiliation National Institute for Health and Welfare and Institute of Health Sciences, University of Oulu, Oulu, Finland

  ⨯
• Stefania Bandinelli,

  Affiliation Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy

  ⨯
• Reiner Biffar,

  Affiliation Department of Prosthetic Dentistry, Gerostomatology, and Dental Materials, University of Greifswald, Greifswald, Germany

  ⨯
• Georg Brabant,

  Affiliation Experimental and Clinical Endocrinology, University of Lübeck, Lübeck, Germany

  ⨯
• David G. Cox,

  Affiliations Cancer Research Center of Lyon, INSERM U1052, Lyon, France, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom

  ⨯
• Yuhui Chen,

  Affiliation Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

  ⨯
• Steven Cummings,

  Affiliation California Pacific Medical Center, San Francisco, California, United States of America

  ⨯
• Luigi Ferrucci,

  Affiliation Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America

  ⨯
• Marc J. Gunter,

  Affiliation Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom

  ⨯
• Susan E. Hankinson,

  Affiliations Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America, Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts, United States of America, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America

  ⨯
• Hannu Martikainen,

  Affiliation Department of Obstetrics and Gynecology, University Hospital of Oulu, Oulu, Finland

  ⨯
• Albert Hofman,

  Affiliations Netherlands Consortium of Healthy Aging, Rotterdam, The Netherlands, Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands

  ⨯
• Georg Homuth,

  Affiliation Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany

  ⨯
• Thomas Illig,

  Affiliations Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany, Hannover Unified Biobank, Hannover Medical School, Hannover, Germany

  ⨯
• John-Olov Jansson,

  Affiliation Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

  ⨯
• Andrew D. Johnson,

  Affiliation National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, United States of America

  ⨯
• David Karasik,

  Affiliation Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, United States of America

  ⨯
• Magnus Karlsson,

  Affiliation Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences and Department of Orthopaedics, Lund University, Malmö, Sweden

  ⨯
• Johannes Kettunen,

  Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

  ⨯
• Douglas P. Kiel,

  Affiliation Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, United States of America

  ⨯
• Peter Kraft,

  Affiliation Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America

  ⨯
• Jingmin Liu,

  Affiliation Women's Health Initiative Clinical Coordinating Center, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America

  ⨯
• Östen Ljunggren,

  Affiliation Department of Medical Sciences, University of Uppsala, Uppsala, Sweden

  ⨯
• Mattias Lorentzon,

  Affiliation Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

  ⨯
• Marcello Maggio,

  Affiliation Department of Internal Medicine and Biomedical Sciences, Section of Geriatrics, University of Parma, Parma, Italy

  ⨯
• Marcello R. P. Markus,

  Affiliation Institute for Community Medicine, University of Greifswald, Greifswald, Germany

  ⨯
• Dan Mellström,

  Affiliation Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

  ⨯
• Iva Miljkovic,

  Affiliation University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America

  ⨯
• Daniel Mirel,

  Affiliation Gene Environment Initiative, Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Boston, Massachusetts, United States of America

  ⨯
• Sarah Nelson,

  Affiliation Department of Biostatistics, University of Washington, Seattle, Washington, United States of America

  ⨯
• Laure Morin Papunen,

  Affiliation Department of Obstetrics and Gynecology, University Hospital of Oulu, Oulu, Finland

  ⨯
• Petra H. M. Peeters,

  Affiliation Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

  ⨯
• Inga Prokopenko,

  Affiliations Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom

  ⨯
• Leslie Raffel,

  Affiliation Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

  ⨯
• Martin Reincke,

  Affiliation Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians University, Munich, Germany

  ⨯
• Alex P. Reiner,

  Affiliation Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America

  ⨯
• Kathryn Rexrode,

  Affiliation Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America

  ⨯
• Fernando Rivadeneira,

  Affiliations Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, Netherlands Consortium of Healthy Aging, Rotterdam, The Netherlands

  ⨯
• Stephen M. Schwartz,

  Affiliation Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America

  ⨯
• David Siscovick,

  Affiliation Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America

  ⨯
• Nicole Soranzo,

  Affiliations Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom

  ⨯
• Doris Stöckl,

  Affiliations Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany, Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University, Munich, Germany

  ⨯
• Shelley Tworoger,

  Affiliations Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America

  ⨯
• André G. Uitterlinden,

  Affiliations Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, Netherlands Consortium of Healthy Aging, Rotterdam, The Netherlands, Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands

  ⨯
• Carla H. van Gils,

  Affiliation Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

  ⨯
• Ramachandran S. Vasan,

  Affiliations Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, United States of America, National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, United States of America

  ⨯
• H.-Erich Wichmann,

  Affiliations Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany, Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany, Klinikum Großhadern, Munich, Germany

  ⨯
• Guangju Zhai,

  Affiliations Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada

  ⨯
• Shalender Bhasin,

  Affiliation Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, Massachusetts, United States of America

  ⨯
• Martin Bidlingmaier,

  Affiliation Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians University, Munich, Germany

  ⨯
• Stephen J. Chanock,

  Affiliation Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America

  ⨯
• Immaculata De Vivo,

  Affiliations Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America

  ⨯
• Tamara B. Harris,

  Affiliation Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, United States of America

  ⨯
• David J. Hunter,

  Affiliations Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America

  ⨯
• Mika Kähönen,

  Affiliation Department of Clinical Physiology, Tampere University Hospital and University of Tampere School of Medicine, Tampere, Finland

  ⨯
• Simin Liu,

  Affiliation Program on Genomics and Nutrition, Department of Epidemiology, University of California Los Angeles, Los Angeles, California, United States of America

  ⨯
• Pamela Ouyang,

  Affiliation Division of Cardiology, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, United States of America

  ⨯
• Tim D. Spector,

  Affiliation Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom

  ⨯
• Yvonne T. van der Schouw,

  Affiliation Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

  ⨯
• Jorma Viikari,

  Affiliation Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland

  ⨯
• Henri Wallaschofski,

  Affiliation Institute for Clinical Chemistry and Laboratory Medicine, University Medicine, Ernst-Moritz-Arndt University of Greifswald, Greifswald, Germany

  ⨯
• Mark I. McCarthy,

  Affiliations Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom, Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom

  ⨯
• Timothy M. Frayling,

  Affiliation Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom

  ⨯
• Anna Murray,

  Affiliation Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom

  ⨯
• Steve Franks,

  Affiliation Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom

  ⨯
• Marjo-Riitta Järvelin ,

  ¶These authors also contributed equally to this work.

  Affiliations Department of Biostatistics and Epidemiology, School of Public Health, MRC-HPA Centre for Environment and Health, Faculty of Medicine, Imperial College London, London, United Kingdom, Institute of Health Sciences, University of Oulu, Oulu, Finland, Biocenter Oulu, University of Oulu, Oulu, Finland, National Institute of Health and Welfare, University of Oulu, Oulu, Finland

  ⨯
• Frank H. de Jong ,

  ¶These authors also contributed equally to this work.

  Affiliation Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

  ⨯
• Olli Raitakari ,

  ¶These authors also contributed equally to this work.

  Affiliation Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital and Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland

  ⨯
• Alexander Teumer ,

  ¶These authors also contributed equally to this work.

  Affiliation Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany

  ⨯
• Claes Ohlsson ,

  ¶These authors also contributed equally to this work.

  Affiliation Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

  ⨯
• Joanne M. Murabito ,

  * E-mail: murabito@bu.edu (JM Murabito); John.perry@pms.ac.uk (JRB Perry)

  ¶These authors also contributed equally to this work.

  Affiliations National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, United States of America, Section of General Internal Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America

  ⨯
•  [ ... ],
• John R. B. Perry

  * E-mail: murabito@bu.edu (JM Murabito); John.perry@pms.ac.uk (JRB Perry)

  ¶These authors also contributed equally to this work.

  Affiliations Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom

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