SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function

*Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland;

†Division of Nephrology and Department of Human Genetics, University of Utah, Salt Lake City, Utah;

‡Division of Genetic Epidemiology, Medical Center – University of Freiburg, Freiburg, Germany;

§Genetics Division,

‖Department of Life and Reproduction Sciences, and

¶Institute for Community Medicine,

**National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts;

††Center for Genomic & Experimental Medicine, Institute of Genetics and Molecular Medicine,

‡‡The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pennsylvania;

§§Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa;

‖‖Center for Biomedicine, European Academy of Bolzano/Bozen, affiliated to the University of Lübeck, Bolzano/Bozen, Italy;

¶¶Department of Biostatistics, Center for Statistical Genetics,

***Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany;

†††Department of Nephrology, University Hospital Regensburg, Regensburg, Germany;

‡‡‡Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere School of Medicine, Tampere, Finland;

§§§Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, Napoli, Italy;

‖‖‖Department of Epidemiology, and

§§§Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, Napoli, Italy;

*Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland;

¶¶¶Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts;

****Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, and

††††Steno Diabetes Center, Gentofte, Denmark;

‡‡‡‡McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland;

‡‡‡‡McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland;

†††Department of Nephrology, University Hospital Regensburg, Regensburg, Germany;

§§§§Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee;

§Genetics Division,

§§§§Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee;

‖‖‖‖Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts;

¶¶¶¶Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois;

‖‖‖Department of Epidemiology, and

*****Survey Research Center, Institute for Social Research, and

†††††Department of Genetics, School of Medicine, Washington University School of Medicine, St. Louis, Missouri;

‡‡‡‡‡Division of Nephrology, Gemelli Foundation University Hospital, Catholic University, Rome, Italy;

§§§§§Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, University of Trieste, Trieste, Italy;

‖‖‖‖‖Division of Preventive Medicine,

***Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany;

¶¶¶¶¶Institute of Genetic Epidemiology and

******Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;

††††††State Key Laboratory of Medical Genomics, Shanghai, China;

‡‡‡‡‡‡Swiss Tropical and Public Health Institute, Basel, Switzerland;

¶¶Department of Biostatistics, Center for Statistical Genetics,

§§§§§§The Charles Bronfman Institute for Personalized Medicine, and

‖‖‖‖‖‖Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan;

¶¶¶¶¶¶Kidney Research Institute,

*******Center for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Westmead, Sydney, New South Wales, Australia;

****Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, and

‡‡‡‡‡‡Swiss Tropical and Public Health Institute, Basel, Switzerland;

†††††††Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland;

‡‡‡‡‡‡‡Department of Epidemiology, and

§§§§§§§Division of Public Health Sciences, Biostatistical Sciences, and

§§§§§§The Charles Bronfman Institute for Personalized Medicine, and

‖‖‖‖‖‖‖Estonian Genome Center of University of Tartu, Tartu, Estonia;

¶¶¶¶¶¶¶Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy;

‖‖‖‖‖‖‖Estonian Genome Center of University of Tartu, Tartu, Estonia;

********Department of Genetics, and

††††††††Department of Epidemiology, Leiden University Medical Center, Leiden, The Netherlands;

‡‡‡‡‡‡‡‡Epidemiology Section, Department of Biostatistics Epidemiology & Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;

§§§§§§§§Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, Italy;

‖‖‖‖‖‖‖‖Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York;

¶¶¶¶¶¶¶¶Department of Health Science, University of Milano, Milano, Italy;

*********Fred Hutchinson Cancer Research Center, Seattle, Washington;

†††††††††Department of Clinical Science, Lund University, Malmö, Sweden;

‡‡‡‡‡‡‡‡‡Icelandic Heart Association, Kopavogur, Iceland;

§§§§§§§§§Faculty of Medicine, University of Iceland, Reykjavik, Iceland;

‖‖‖‖‖‖Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan;

‖‖‖‖‖‖‖‖‖San Raffaele Scientific Institute, Milano, Italy;

¶¶¶¶¶¶¶¶¶Program in Personalized and Genomic Medicine and Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland;

‖‖‖‖‖‖Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan;

**********Department of Medicine and Department of Biomedical Sciences, and

††††††††††Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California;

‡‡‡‡‡‡‡‡‡‡Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University, St. Louis, Missouri;

**National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts;

§§§§§§§§§§Department of Epidemiology, Fairbanks School of Public Health, Indianapolis, Indiana;

‖‖‖‖‖‖‖‖‖‖Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana;

¶¶¶¶¶¶¶¶¶¶The Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas;

†††††Department of Genetics, School of Medicine, Washington University School of Medicine, St. Louis, Missouri;

****Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, and

§§§§§§The Charles Bronfman Institute for Personalized Medicine, and

¶¶¶¶¶¶¶¶Department of Health Science, University of Milano, Milano, Italy;

***********Department of Clinical Biochemistry, and

†††††††††††Cardiovascular Health Research Unit, Department of Medicine, and

††Center for Genomic & Experimental Medicine, Institute of Genetics and Molecular Medicine,

‡‡The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pennsylvania;

‡‡‡‡‡‡‡‡‡‡‡Department of Internal Medicine and Endocrinology, Vejle Hospital, Vejle, Denmark;

*Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland;

§§§§§§§§§§§Department of Medicine, University of South Alabama College of Medicine, Mobile, Alabama;

‖‖‖‖‖‖‖‖‖‖‖Renal Division and Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts;

¶¶¶¶¶¶¶¶Department of Health Science, University of Milano, Milano, Italy;

¶¶¶¶¶¶¶¶¶¶¶Division of Nephrology, San Paolo Hospital, Milan, Italy;

¶¶¶¶¶¶Kidney Research Institute,

************Division of Nephrology, Department of Medicine, Leiden University Medical Center and Leiden University, The Netherlands;

§§§§Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee;

††††††††††††University of Zurich, Institute of Physiology, Zurich Center for Integrative Human Physiology, Mechanisms of Inherited Kidney Disorders Group, Zürich, Switzerland;

‡‡‡‡‡‡‡‡‡‡‡‡Department of Medicine, University of Mississippi, Jackson, Mississippi;

§§§§§§§§§§§§Department of Anatomy and Cell Biology,

‡‡‡‡McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland;

‖‖‖‖‖‖‖Estonian Genome Center of University of Tartu, Tartu, Estonia;

‖‖‖‖‖‖‖‖‖‖‖‖Division of Endocrinology, Children's Hospital Boston, Boston, Massachusetts;

¶¶¶¶¶¶¶¶¶¶¶¶Department of Genetics, Harvard Medical School, Boston, Massachusetts;

‖‖‖Department of Epidemiology, and

‡‡‡‡‡‡‡‡‡‡‡‡Department of Medicine, University of Mississippi, Jackson, Mississippi;

*************Department of Medical Genetics and Molecular Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania;

†††††††††††††Research Center for Prevention and Health, The Capital Region of Denmark, Glostrup University Hospital, Glostrup, Denmark;

§§§§§§The Charles Bronfman Institute for Personalized Medicine, and

****Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, and

‡‡‡‡‡‡‡‡‡Icelandic Heart Association, Kopavogur, Iceland;

****Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, and

‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;

‡‡‡‡‡‡‡‡‡‡‡‡‡National Institutes on Aging, Bethesda, Maryland;

††Center for Genomic & Experimental Medicine, Institute of Genetics and Molecular Medicine,

§§§§§§§§§§§§§Medical Research Council Human Genetics, Institute of Genetics and Molecular Medicine, and

‖‖‖‖‖‖‖‖‖‖‖‖‖Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, United Kindom;

‖‖‖Department of Epidemiology, and

¶¶¶¶¶¶¶¶¶¶¶¶¶Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts;

†††††††††††††Research Center for Prevention and Health, The Capital Region of Denmark, Glostrup University Hospital, Glostrup, Denmark;

**************Department of Internal Medicine, The Ohio State University, Columbia, Ohio;

†††††††††††††Research Center for Prevention and Health, The Capital Region of Denmark, Glostrup University Hospital, Glostrup, Denmark;

††††Steno Diabetes Center, Gentofte, Denmark;

†††Department of Nephrology, University Hospital Regensburg, Regensburg, Germany;

‖‖‖‖‖‖Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan;

††††††††††††††Department of Internal Medicine II, Cardiology, University of Ulm Medical Center, Ulm, Germany;

‡‡‡‡‡‡‡‡‡‡‡‡‡‡The German Heart Center Munich, Technical University of Munich, Munich, Germany;

§§§§§§§§§§§§§§German Center for Cardiovascular Research, partner site Munich Heart Alliance, Munich, Germany;

*********Fred Hutchinson Cancer Research Center, Seattle, Washington;

¶¶¶¶¶¶¶¶¶¶¶¶¶¶Research Unit of Molecular Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany;

¶¶¶¶¶¶¶¶¶¶¶¶¶¶Research Unit of Molecular Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany;

‡‡‡‡‡‡‡‡‡‡‡‡‡National Institutes on Aging, Bethesda, Maryland;

***************Department of General Practice, Aarhus University, Aarhus, Denmark;

‡‡‡Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere School of Medicine, Tampere, Finland;

**National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts;

††Center for Genomic & Experimental Medicine, Institute of Genetics and Molecular Medicine,

†††††††††††††Research Center for Prevention and Health, The Capital Region of Denmark, Glostrup University Hospital, Glostrup, Denmark;

†††††††††††††††Department of Clinical Experimental Research, Rigshospitalet, Denmark;

‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;

§§§§§§§§§§§§§§§Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina;

§§§§§§The Charles Bronfman Institute for Personalized Medicine, and

‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖Renal Unit, Department of Medicine, University Hospital of Verona, Verona, Italy;

¶¶¶¶¶¶¶¶¶¶¶¶¶¶Research Unit of Molecular Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany;

†††††††††Department of Clinical Science, Lund University, Malmö, Sweden;

‖‖‖‖‖‖‖Estonian Genome Center of University of Tartu, Tartu, Estonia;

*******Center for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Westmead, Sydney, New South Wales, Australia;

¶¶¶¶¶¶¶¶¶¶¶¶¶¶¶Institute of Clinical Chemistry and Laboratory Medicine,

****************German Center for Cardiovascular Research, partner site Greifswald, Greifswald, Germany;

††††††††††††††††Cologne Center for Genomics, University of Cologne, Cologne, Germany;

†††††††††Department of Clinical Science, Lund University, Malmö, Sweden;

‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;

****Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, and

¶¶¶¶¶¶¶¶¶¶¶¶¶¶Research Unit of Molecular Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany;

¶¶¶¶¶¶¶¶¶¶¶¶¶¶Research Unit of Molecular Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany;

§§§§§§§§§§§§§§§§German Center for Cardiovascular Disease Research, Munich, Germany;

*********Fred Hutchinson Cancer Research Center, Seattle, Washington;

‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖Center for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom;

††Center for Genomic & Experimental Medicine, Institute of Genetics and Molecular Medicine,

‡‡‡‡‡‡Swiss Tropical and Public Health Institute, Basel, Switzerland;

†††††††††††Cardiovascular Health Research Unit, Department of Medicine, and

¶¶¶¶¶¶¶¶¶¶¶¶¶¶¶¶Departments of Epidemiology and Health Services, University of Washington, Seattle, Washington;

*****************Group Health Research Institute, Group Health Cooperative, Seattle, Washington;

¶¶¶¶¶¶¶¶¶¶¶¶¶Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts;

†††††††††††††††††Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, and Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland;

*********Fred Hutchinson Cancer Research Center, Seattle, Washington;

‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡Institute of Physiology, and

‖‖‖‖‖Division of Preventive Medicine,

§§§§§§§§§§§§§§§§§Cardiovascular Medicine Division, and

‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands;

¶¶¶¶¶¶¶¶¶¶¶¶¶¶¶¶¶National Heart, Lung, and Blood Institute, Bethesda, Maryland;

******************Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany;

†††††††††††Cardiovascular Health Research Unit, Department of Medicine, and

¶¶¶¶¶¶¶Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy;

¶¶¶¶¶¶¶¶¶¶¶¶¶¶Research Unit of Molecular Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany;

††††††††††††††††††Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany;

‖‖‖‖‖‖‖‖‖San Raffaele Scientific Institute, Milano, Italy;

‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota;

‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands;

§§§§§§§§Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, Italy;

¶¶¶¶¶¶¶¶Department of Health Science, University of Milano, Milano, Italy;

****************German Center for Cardiovascular Research, partner site Greifswald, Greifswald, Germany;

******************Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany;

¶Institute for Community Medicine,

****************German Center for Cardiovascular Research, partner site Greifswald, Greifswald, Germany;

§§§§§§§§§§§§§§§§§§German Center for Diabetes Research, partner site Greifswald, Greifswald, Germany;

¶¶¶¶¶¶¶¶¶¶¶¶¶¶Research Unit of Molecular Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany;

¶¶¶¶¶¶¶¶¶¶¶¶¶¶Research Unit of Molecular Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany;

*******Center for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Westmead, Sydney, New South Wales, Australia;

*****Survey Research Center, Institute for Social Research, and

‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖‖Department of Public Health, Aarhus University, Aarhus, Denmark;

‡‡The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pennsylvania;

§§Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa;

**National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts;

¶¶¶¶¶¶¶¶¶¶¶¶¶¶¶¶¶¶Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina;

§Genetics Division,

††††Steno Diabetes Center, Gentofte, Denmark;

*******************Harvard Stem Cell Institute, Cambridge, Massachusetts; and

†††††††††††††††††††Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;

‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡‡Dana-Farber Cancer Institute, Boston, Massachusetts

*Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland;

‡Division of Genetic Epidemiology, Medical Center – University of Freiburg, Freiburg, Germany;

**National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts;

‖‖‖‖‖Division of Preventive Medicine,