A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol Ida Surakka1,2., Aaron Isaacs3,4., Lennart C. Karssen 3 , Pirkka-Pekka P. Laurila1,2,5, Rita P. S. Middelberg6,7, Emmi Tikkanen1,2, Janina S. Ried8, Claudia Lamina9, Massimo Mangino10, Wilmar Igl11, Jouke-Jan Hottenga12, Vasiliki Lagou13,14, Pim van der Harst15, Irene Mateo Leach15, To˜ nu Esko16,17, Zolta´ n Kutalik18,19, Nicholas W. Wainwright20,21, Maksim V. Struchalin 3 , Antti-Pekka Sarin1,2, Antti J. Kangas22, Jorma S. Viikari23, Markus Perola1,2,16, Taina Rantanen24, Ann-Kristin Petersen8, Pasi Soininen25, A˚ sa Johansson11, Nicole Soranzo10,20, Andrew C. Heath26, Theodore Papamarkou20,21, Inga Prokopenko13,14, Anke To¨ njes27,28, Florian Kronenberg9, Angela Do¨ ring29,30, Fernando Rivadeneira31,32,33, Grant W. Montgomery6, John B. Whitfield6, Mika Ka¨ ho¨ nen34,35, Terho Lehtima¨ ki35,36, Nelson B. Freimer37,38, Gonneke Willemsen12, Eco J. C. de Geus12, Aarno Palotie1,5,20,39, Manj S. Sandhu20,21, Dawn M. Waterworth40, Andres Metspalu16,17,41, Michael Stumvoll42, Andre´ G. Uitterlinden31,32,33, Antti Jula43, Gerjan Navis44, Cisca Wijmenga45, Bruce H. R. Wolffenbuttel46, Marja- Riitta Taskinen47, Mika Ala-Korpela22,25,48, Jaakko Kaprio1,49,50, Kirsten O. Kyvik51,52, Dorret I. Boomsma12, Nancy L. Pedersen53, Ulf Gyllensten11, James F. Wilson54, Igor Rudan54,55, Harry Campbell54, Peter P. Pramstaller56,57,58,59, Tim D. Spector10, Jacqueline C. M. Witteman31,32,33, Johan G. Eriksson60,61,62,63,64, Veikko Salomaa65, Ben A. Oostra66, Olli T. Raitakari67,68, H.-Erich Wichmann29,69,70, Christian Gieger8, Marjo-Riitta Ja¨ rvelin71, Nicholas G. Martin6, Albert Hofman31,32,33, Mark I. McCarthy13,14,72, Leena Peltonen1,2,5,18,39{, Cornelia M. van Duijn3,4,33, Yurii S. Aulchenko3", Samuli Ripatti1,2,20"*, for the ENGAGE Consortium 1 Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, 2 Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland, 3 Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands, 4 Centre for Medical Systems Biology, Netherlands Genomics Initiative, Leiden, The Netherlands, 5 Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, 6 Queensland Institute of Medical Research, Brisbane, Australia, 7 Department of Medicine, Prince Charles Hospital, Chermside, Australia, 8 Institute of Genetic Epidemiology, Helmholtz Zentrum Mu¨ nchen – German Research Center for Environmental Health, Neuherberg, Germany, 9 Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria, 10 Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom, 11 Department of Immunology, Genetics, and Pathology, University of Uppsala, Uppsala, Sweden, 12 Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands, 13 Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom, 14 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, 15 Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 16 The Estonian Genome Center and the Center of Translational Genomics of the University of Tartu, Tartu, Estonia, 17 The Institute of Molecular and Cellular Biology of the University of Tartu, Tartu, Estonia, 18 Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland, 19 Swiss Institute of Bioinformatics, Lausanne, Switzerland, 20 Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom, 21 Non-Communicable Disease Research Group, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom, 22 Computational Medicine Research Group, Institute of Clinical Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland, 23 Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland, 24 Department of Health Sciences, Gerontology Research Centre, University of Jyva¨skyla¨, Jyva¨skyla¨, Finland, 25 NMR Metabonomics Laboratory, Department of Biosciences, University of Eastern Finland, Kuopio, Finland, 26 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America, 27 Medical Department, University of Leipzig, Leipzig, Germany, 28 IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany, 29 Institute of Epidemiology I, Helmholtz Zentrum Mu¨ nchen – German Research Center for Environmental Health, Neuherberg, Germany, 30 Institute of Epidemiology II, Helmholtz Zentrum Mu¨ nchen – German Research Center for Environmental Health, Neuherberg, Germany, 31 Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands, 32 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, 33 Netherlands Genomics Initiative (NGI)–sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands, 34 Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland, 35 Medical School, University of Tampere, Tampere, Finland, 36 Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland, 37 Department of Psychiatry, University of California Los Angeles, Los Angeles, United States of America, 38 Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, United States of America, 39 The Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America, 40 Genetics, Medicines Discovery, and Development, GlaxoSmithKline, Philadelphia, Pennsylvania, United States of America, 41 The Estonian Biocentre, Tartu, Estonia, 42 Department of Medicine, University of Leipzig, Leipzig, Germany, 43 Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland, 44 Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 45 Department of Genetics, University Medical Centre Groningen and University of Groningen, Groningen, The Netherlands, 46 Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 47 Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland, 48 Department of Internal Medicine and Biocenter Oulu, Clinical Research Center, University of Oulu, Oulu, Finland, 49 Department of Public Health, University of Helsinki, Helsinki, Finland, 50 Unit for Child and Adolescent Mental Health, National Institute for Health and Welfare, Helsinki, Finland, 51 Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark, 52 Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark, 53 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, 54 Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom, 55 Croatian Centre for Global Health, University of Split Medical School, Split, Croatia, 56 Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), PLoS Genetics | www.plosgenetics.org 1 October 2011 | Volume 7 | Issue 10 | e1002333