A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

• Ida Surakka ,

  Contributed equally to this work with: Ida Surakka, Aaron Isaacs

  Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland

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• Aaron Isaacs ,

  Contributed equally to this work with: Ida Surakka, Aaron Isaacs

  Affiliations Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands, Centre for Medical Systems Biology, Netherlands Genomics Initiative, Leiden, The Netherlands

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• Lennart C. Karssen,

  Affiliation Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

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• Pirkka-Pekka P. Laurila,

  Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland, Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

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• Rita P. S. Middelberg,

  Affiliations Queensland Institute of Medical Research, Brisbane, Australia, Department of Medicine, Prince Charles Hospital, Chermside, Australia

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• Emmi Tikkanen,

  Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland

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• Janina S. Ried,

  Affiliation Institute of Genetic Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

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• Claudia Lamina,

  Affiliation Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria

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• Massimo Mangino,

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

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• Wilmar Igl,

  Affiliation Department of Immunology, Genetics, and Pathology, University of Uppsala, Uppsala, Sweden

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• Jouke-Jan Hottenga,

  Affiliation Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands

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• Vasiliki Lagou,

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

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• Pim van der Harst,

  Affiliation Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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• Irene Mateo Leach,

  Affiliation Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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• Tõnu Esko,

  Affiliations The Estonian Genome Center and the Center of Translational Genomics of the University of Tartu, Tartu, Estonia, The Institute of Molecular and Cellular Biology of the University of Tartu, Tartu, Estonia

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• Zoltán Kutalik,

  Affiliations Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland, Swiss Institute of Bioinformatics, Lausanne, Switzerland

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• Nicholas W. Wainwright,

  Affiliations Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom, Non-Communicable Disease Research Group, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom

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• Maksim V. Struchalin,

  Affiliation Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

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• Antti-Pekka Sarin,

  Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland

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• Antti J. Kangas,

  Affiliation Computational Medicine Research Group, Institute of Clinical Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland

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• Jorma S. Viikari,

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

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• Markus Perola,

  Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland, The Estonian Genome Center and the Center of Translational Genomics of the University of Tartu, Tartu, Estonia

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• Taina Rantanen,

  Affiliation Department of Health Sciences, Gerontology Research Centre, University of Jyväskylä, Jyväskylä, Finland

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• Ann-Kristin Petersen,

  Affiliation Institute of Genetic Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

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• Pasi Soininen,

  Affiliation NMR Metabonomics Laboratory, Department of Biosciences, University of Eastern Finland, Kuopio, Finland

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• Åsa Johansson,

  Affiliation Department of Immunology, Genetics, and Pathology, University of Uppsala, Uppsala, Sweden

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• Nicole Soranzo,

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

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• Andrew C. Heath,

  Affiliation Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America

  ⨯
• Theodore Papamarkou,

  Affiliations Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom, Non-Communicable Disease Research Group, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Inga Prokopenko,

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

  ⨯
• Anke Tönjes,

  Affiliations Medical Department, University of Leipzig, Leipzig, Germany, IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany

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• Florian Kronenberg,

  Affiliation Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria

  ⨯
• Angela Döring,

  Affiliations Institute of Epidemiology I, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany, Institute of Epidemiology II, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

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• Fernando Rivadeneira,

  Affiliations Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, Netherlands Genomics Initiative (NGI)–sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands

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• Grant W. Montgomery,

  Affiliation Queensland Institute of Medical Research, Brisbane, Australia

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• John B. Whitfield,

  Affiliation Queensland Institute of Medical Research, Brisbane, Australia

  ⨯
• Mika Kähönen,

  Affiliations Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland, Medical School, University of Tampere, Tampere, Finland

  ⨯
• Terho Lehtimäki,

  Affiliations Medical School, University of Tampere, Tampere, Finland, Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland

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• Nelson B. Freimer,

  Affiliations Department of Psychiatry, University of California Los Angeles, Los Angeles, United States of America, Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, United States of America

  ⨯
• Gonneke Willemsen,

  Affiliation Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands

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• Eco J. C. de Geus,

  Affiliation Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands

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• Aarno Palotie,

  Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom, The Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America

  ⨯
• Manj S. Sandhu,

  Affiliations Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom, Non-Communicable Disease Research Group, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom

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• Dawn M. Waterworth,

  Affiliation Genetics, Medicines Discovery, and Development, GlaxoSmithKline, Philadelphia, Pennsylvania, United States of America

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• Andres Metspalu,

  Affiliations The Estonian Genome Center and the Center of Translational Genomics of the University of Tartu, Tartu, Estonia, The Institute of Molecular and Cellular Biology of the University of Tartu, Tartu, Estonia, The Estonian Biocentre, Tartu, Estonia

  ⨯
• Michael Stumvoll,

  Affiliation Department of Medicine, University of Leipzig, Leipzig, Germany

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• André G. Uitterlinden,

  Affiliations Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, Netherlands Genomics Initiative (NGI)–sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands

  ⨯
• Antti Jula,

  Affiliation Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland

  ⨯
• Gerjan Navis,

  Affiliation Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

  ⨯
• Cisca Wijmenga,

  Affiliation Department of Genetics, University Medical Centre Groningen and University of Groningen, Groningen, The Netherlands

  ⨯
• Bruce H. R. Wolffenbuttel,

  Affiliation Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

  ⨯
• Marja-Riitta Taskinen,

  Affiliation Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

  ⨯
• Mika Ala-Korpela,

  Affiliations Computational Medicine Research Group, Institute of Clinical Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland, NMR Metabonomics Laboratory, Department of Biosciences, University of Eastern Finland, Kuopio, Finland, Department of Internal Medicine and Biocenter Oulu, Clinical Research Center, University of Oulu, Oulu, Finland

  ⨯
• Jaakko Kaprio,

  Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Department of Public Health, University of Helsinki, Helsinki, Finland, Unit for Child and Adolescent Mental Health, National Institute for Health and Welfare, Helsinki, Finland

  ⨯
• Kirsten O. Kyvik,

  Affiliations Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark, Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark

  ⨯
• Dorret I. Boomsma,

  Affiliation Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands

  ⨯
• Nancy L. Pedersen,

  Affiliation Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

  ⨯
• Ulf Gyllensten,

  Affiliation Department of Immunology, Genetics, and Pathology, University of Uppsala, Uppsala, Sweden

  ⨯
• James F. Wilson,

  Affiliation Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom

  ⨯
• Igor Rudan,

  Affiliations Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom, Croatian Centre for Global Health, University of Split Medical School, Split, Croatia

  ⨯
• Harry Campbell,

  Affiliation Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom

  ⨯
• Peter P. Pramstaller,

  Affiliations Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, Affiliated Institute of the University of Lübeck, Lübeck, Germany, Department of Neurology, University of Lübeck, Lübeck, Germany, Department of Neurology, Central Hospital of Bolzano, Bolzano, Italy

  ⨯
• Tim D. Spector,

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

  ⨯
• Jacqueline C. M. Witteman,

  Affiliations Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, Netherlands Genomics Initiative (NGI)–sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands

  ⨯
• Johan G. Eriksson,

  Affiliations Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland, Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland, Folkhälsan Research Centre, Helsinki, Finland, Vasa Central Hospital, Vasa, Finland, Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

  ⨯
• Veikko Salomaa,

  Affiliation Unit of Chronic Disease Epidemiology and Prevention, National Institute for Health and Welfare, Helsinki, Finland

  ⨯
• Ben A. Oostra,

  Affiliation Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands

  ⨯
• Olli T. Raitakari,

  Affiliations Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Clinical Physiology, University of Turku and Turku University Hospital, Turku, Finland

  ⨯
• H.-Erich Wichmann,

  Affiliations Institute of Epidemiology I, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany, Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany, Klinikum Grosshadern, Munich, Germany

  ⨯
• Christian Gieger,

  Affiliation Institute of Genetic Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

  ⨯
• Marjo-Riitta Järvelin,

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

  ⨯
• Nicholas G. Martin,

  Affiliation Queensland Institute of Medical Research, Brisbane, Australia

  ⨯
• Albert Hofman,

  Affiliations Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, Netherlands Genomics Initiative (NGI)–sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands

  ⨯
• Mark I. McCarthy,

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

  ⨯
• Leena Peltonen †,

  † Deceased.

  Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland, Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland, The Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America

  ⨯
• Cornelia M. van Duijn,

  Affiliations Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands, Centre for Medical Systems Biology, Netherlands Genomics Initiative, Leiden, The Netherlands, Netherlands Genomics Initiative (NGI)–sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands

  ⨯
• Yurii S. Aulchenko ,

  ¶These authors also contributed equally to this work.

  Affiliation Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

  ⨯
• Samuli Ripatti ,

  * E-mail: samuli.ripatti@fimm.fi

  ¶These authors also contributed equally to this work.

  Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland, Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom

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