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Open Access
Peer-reviewed
Research Article
Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population
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Elaine T. Lim,
Affiliations Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America, Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, United States of America
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Peter Würtz,
Affiliations Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland
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Aki S. Havulinna,
Affiliation Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
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Priit Palta,
Affiliations Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
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Taru Tukiainen,
Affiliations Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
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Karola Rehnström,
Affiliation Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
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Tõnu Esko,
Affiliations Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America, Estonian Genome Center, University of Tartu, Tartu, Estonia, Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Children's Hospital Boston, Boston, Massachusetts, United States of America
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Reedik Mägi,
Affiliation Estonian Genome Center, University of Tartu, Tartu, Estonia
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Michael Inouye,
Affiliation Medical Systems Biology, Department of Pathology and Department of Microbiology & Immunology, The University of Melbourne, Parkville, Victoria, Australia
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Tuuli Lappalainen,
Affiliations Department of Genetics, Stanford University, Stanford, California, United States of America, Stanford Center for Computational, Evolutionary and Human Genomics, Stanford, California, United States of America
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Yingleong Chan,
Affiliations Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, United States of America, Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Children's Hospital Boston, Boston, Massachusetts, United States of America
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Rany M. Salem,
Affiliations Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Children's Hospital Boston, Boston, Massachusetts, United States of America
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Monkol Lek,
Affiliations Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
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Jason Flannick,
Affiliations Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
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Xueling Sim,
Affiliation Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, United States of America
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Alisa Manning,
Affiliation Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America
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Claes Ladenvall,
Affiliations Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, Lund University Diabetes Center, Department of Clinical Sciences, Diabetes & Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden
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Suzannah Bumpstead,
Affiliation Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
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Eija Hämäläinen,
Affiliations Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
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Kristiina Aalto,
Affiliation MediCity, University of Turku, Turku, Finland
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Mikael Maksimow,
Affiliation MediCity, University of Turku, Turku, Finland
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Marko Salmi,
Affiliation Department of Medical Microbiology and Immunology, University of Turku and National Institute for Health and Welfare, Turku, Finland
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Stefan Blankenberg,
Affiliations University Heart Centre Hamburg, Clinic for General and Interventional Cardiology, Hamburg, Germany, DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany
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Diego Ardissino,
Affiliation Division of Cardiology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
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Svati Shah,
Affiliation Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America
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Benjamin Horne,
Affiliation Intermountain Heart Institute, Intermountain Medical Center, Salt Lake City, Utah, United States of America
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Ruth McPherson,
Affiliation Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
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Gerald K. Hovingh,
Affiliation Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
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Muredach P. Reilly,
Affiliation Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
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Hugh Watkins,
Affiliation Division of Cardiovascular Medicine, Radcliffe Department of Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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Anuj Goel,
Affiliation Division of Cardiovascular Medicine, Radcliffe Department of Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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Martin Farrall,
Affiliation Division of Cardiovascular Medicine, Radcliffe Department of Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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Domenico Girelli,
Affiliation University of Verona School of Medicine, Department of Medicine, Verona, Italy
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Alex P. Reiner,
Affiliation Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
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Nathan O. Stitziel,
Affiliation Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
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Sekar Kathiresan,
Affiliation Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
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Stacey Gabriel,
Affiliation Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America
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Jeffrey C. Barrett,
Affiliation Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
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Terho Lehtimäki,
Affiliation Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere School of Medicine, Tampere, Finland
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Markku Laakso,
Affiliation Department of Medicine, University of Eastern Finland, Kuopio, Finland
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Leif Groop,
Affiliations Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, Lund University Diabetes Center, Department of Clinical Sciences, Diabetes & Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden
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Jaakko Kaprio,
Affiliations Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, University of Helsinki, Hjelt Institute, Dept of Public Health, Helsinki, Finland, National Institute for Health and Welfare, Dept of Mental Health and Substance Abuse Services, Helsinki, Finland
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Markus Perola,
Affiliation Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
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Mark I. McCarthy,
Affiliations Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, United Kingdom, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, Oxford NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, United Kingdom
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Michael Boehnke,
Affiliation Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, United States of America
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David M. Altshuler,
Affiliations Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
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Cecilia M. Lindgren,
Affiliations Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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Joel N. Hirschhorn,
Affiliations Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Children's Hospital Boston, Boston, Massachusetts, United States of America
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Andres Metspalu,
Affiliation Estonian Genome Center, University of Tartu, Tartu, Estonia
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Nelson B. Freimer,
Affiliation University of California Los Angeles Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California, United States of America
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Tanja Zeller,
Affiliations University Heart Centre Hamburg, Clinic for General and Interventional Cardiology, Hamburg, Germany, DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany
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Sirpa Jalkanen,
Affiliation Department of Medical Microbiology and Immunology, University of Turku and National Institute for Health and Welfare, Turku, Finland
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Seppo Koskinen,
Affiliation Department of Health, Functional Capacity and Welfare, National Institute for Health and Welfare, Helsinki, Finland
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Olli Raitakari,
Affiliations Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
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Richard Durbin,
Affiliation Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
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Daniel G. MacArthur,
Affiliations Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
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Veikko Salomaa,
Affiliation Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
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Samuli Ripatti,
Affiliations Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom, University of Helsinki, Hjelt Institute, Dept of Public Health, Helsinki, Finland, Department of Biometry, Hjelt Institute, University of Helsinki, Helsinki, Finland
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Mark J. Daly ,
Contributed equally to this work with: Mark J. Daly, Aarno Palotie
* E-mail: mjdaly@atgu.mgh.harvard.edu (MJD); aarno@broadinstitute.org (AP)
Affiliations Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
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Aarno Palotie ,
Contributed equally to this work with: Mark J. Daly, Aarno Palotie
* E-mail: mjdaly@atgu.mgh.harvard.edu (MJD); aarno@broadinstitute.org (AP)
Affiliations Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, United States of America
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- for the Sequencing Initiative Suomi (SISu) Project
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Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population
- Elaine T. Lim,
- Peter Würtz,
- Aki S. Havulinna,
- Priit Palta,
- Taru Tukiainen,
- Karola Rehnström,
- Tõnu Esko,
- Reedik Mägi,
- Michael Inouye,
- Tuuli Lappalainen
- Published: July 31, 2014
- https://doi.org/10.1371/journal.pgen.1004494