La maladie de Parkinson en France (serveur d'exploration)

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<title xml:lang="en">Diagnosis of Parkinson’s disease on the basis of clinical–genetic classification: a population-based modelling study</title>
<author>
<name sortKey="Nalls, Mike A" sort="Nalls, Mike A" uniqKey="Nalls M" first="Mike A." last="Nalls">Mike A. Nalls</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mclean, Cory Y" sort="Mclean, Cory Y" uniqKey="Mclean C" first="Cory Y." last="Mclean">Cory Y. Mclean</name>
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<nlm:aff id="A2">23andMe, Inc., Mountain View, CA, USA</nlm:aff>
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<author>
<name sortKey="Rick, Jacqueline" sort="Rick, Jacqueline" uniqKey="Rick J" first="Jacqueline" last="Rick">Jacqueline Rick</name>
<affiliation>
<nlm:aff id="A3">Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Eberly, Shirley" sort="Eberly, Shirley" uniqKey="Eberly S" first="Shirley" last="Eberly">Shirley Eberly</name>
<affiliation>
<nlm:aff id="A4">Department of Biostatistics, University of Rochester Medical Center, Rochester, NY, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Hutten, Samantha J" sort="Hutten, Samantha J" uniqKey="Hutten S" first="Samantha J." last="Hutten">Samantha J. Hutten</name>
<affiliation>
<nlm:aff id="A5">The Michael J. Fox Foundation for Parkinson’s Research, New York, NY 10018, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gwinn, Katrina" sort="Gwinn, Katrina" uniqKey="Gwinn K" first="Katrina" last="Gwinn">Katrina Gwinn</name>
<affiliation>
<nlm:aff id="A6">National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sutherland, Margaret" sort="Sutherland, Margaret" uniqKey="Sutherland M" first="Margaret" last="Sutherland">Margaret Sutherland</name>
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<nlm:aff id="A6">National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
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<author>
<name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name>
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<nlm:aff id="A7">INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A8">Paul Sabatier University, Toulouse, France</nlm:aff>
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<author>
<name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name>
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<nlm:aff id="A9">Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Williams, Nigel" sort="Williams, Nigel" uniqKey="Williams N" first="Nigel" last="Williams">Nigel Williams</name>
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<nlm:aff id="A10">Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales</nlm:aff>
</affiliation>
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<author>
<name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name>
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<nlm:aff id="A11">Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name>
<affiliation>
<nlm:aff id="A12">Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name>
<affiliation>
<nlm:aff id="A13">Sorbonne Université, UPMC Univ Paris 06, UM 1127, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A14">Inserm, U 1127, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A15">Cnrs, UMR 7225, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A16">ICM, Paris, F-75013 Paris, France</nlm:aff>
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<affiliation>
<nlm:aff id="A17">AP-HP, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, F-75013, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Price, T Ryan" sort="Price, T Ryan" uniqKey="Price T" first="T. Ryan" last="Price">T. Ryan Price</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Nicolas, Aude" sort="Nicolas, Aude" uniqKey="Nicolas A" first="Aude" last="Nicolas">Aude Nicolas</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Keller, Margaux F" sort="Keller, Margaux F" uniqKey="Keller M" first="Margaux F." last="Keller">Margaux F. Keller</name>
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<nlm:aff id="A18">Genetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Molony, Cliona" sort="Molony, Cliona" uniqKey="Molony C" first="Cliona" last="Molony">Cliona Molony</name>
<affiliation>
<nlm:aff id="A18">Genetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gibbs, J Raphael" sort="Gibbs, J Raphael" uniqKey="Gibbs J" first="J. Raphael" last="Gibbs">J. Raphael Gibbs</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Chen Plotkin, Alice" sort="Chen Plotkin, Alice" uniqKey="Chen Plotkin A" first="Alice" last="Chen-Plotkin">Alice Chen-Plotkin</name>
<affiliation>
<nlm:aff id="A3">Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Suh, Eunran" sort="Suh, Eunran" uniqKey="Suh E" first="Eunran" last="Suh">Eunran Suh</name>
<affiliation>
<nlm:aff id="A19">Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Letson, Christopher" sort="Letson, Christopher" uniqKey="Letson C" first="Christopher" last="Letson">Christopher Letson</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Fiandaca, Massimo S" sort="Fiandaca, Massimo S" uniqKey="Fiandaca M" first="Massimo S." last="Fiandaca">Massimo S. Fiandaca</name>
<affiliation>
<nlm:aff id="A20">Department of Neurology, Georgetown University Medical Center, DC, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mapstone, Mark" sort="Mapstone, Mark" uniqKey="Mapstone M" first="Mark" last="Mapstone">Mark Mapstone</name>
<affiliation>
<nlm:aff id="A21">Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Federoff, Howard J" sort="Federoff, Howard J" uniqKey="Federoff H" first="Howard J." last="Federoff">Howard J. Federoff</name>
<affiliation>
<nlm:aff id="A20">Department of Neurology, Georgetown University Medical Center, DC, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Noyce, Alastair J" sort="Noyce, Alastair J" uniqKey="Noyce A" first="Alastair J" last="Noyce">Alastair J. Noyce</name>
<affiliation>
<nlm:aff id="A11">Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Morris, Huw" sort="Morris, Huw" uniqKey="Morris H" first="Huw" last="Morris">Huw Morris</name>
<affiliation>
<nlm:aff id="A11">Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Van Deerlin, Vivianna M" sort="Van Deerlin, Vivianna M" uniqKey="Van Deerlin V" first="Vivianna M." last="Van Deerlin">Vivianna M. Van Deerlin</name>
<affiliation>
<nlm:aff id="A19">Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Weintraub, Daniel" sort="Weintraub, Daniel" uniqKey="Weintraub D" first="Daniel" last="Weintraub">Daniel Weintraub</name>
<affiliation>
<nlm:aff id="A3">Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A22">Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Zabetian, Cyrus" sort="Zabetian, Cyrus" uniqKey="Zabetian C" first="Cyrus" last="Zabetian">Cyrus Zabetian</name>
<affiliation>
<nlm:aff id="A23">Department of Neurology; Division of Neurogenetics; Staff Neurologist, VA Puget Sound Health Care System, Seattle, WA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Hernandez, Dena G" sort="Hernandez, Dena G" uniqKey="Hernandez D" first="Dena G." last="Hernandez">Dena G. Hernandez</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name>
<affiliation>
<nlm:aff id="A13">Sorbonne Université, UPMC Univ Paris 06, UM 1127, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A14">Inserm, U 1127, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A15">Cnrs, UMR 7225, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A16">ICM, Paris, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A17">AP-HP, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, F-75013, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mullins, Meghan" sort="Mullins, Meghan" uniqKey="Mullins M" first="Meghan" last="Mullins">Meghan Mullins</name>
<affiliation>
<nlm:aff id="A2">23andMe, Inc., Mountain View, CA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Conley, Emily Drabant" sort="Conley, Emily Drabant" uniqKey="Conley E" first="Emily Drabant" last="Conley">Emily Drabant Conley</name>
<affiliation>
<nlm:aff id="A2">23andMe, Inc., Mountain View, CA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Northover, Carrie" sort="Northover, Carrie" uniqKey="Northover C" first="Carrie" last="Northover">Carrie Northover</name>
<affiliation>
<nlm:aff id="A2">23andMe, Inc., Mountain View, CA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Frasier, Mark" sort="Frasier, Mark" uniqKey="Frasier M" first="Mark" last="Frasier">Mark Frasier</name>
<affiliation>
<nlm:aff id="A5">The Michael J. Fox Foundation for Parkinson’s Research, New York, NY 10018, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Marek, Ken" sort="Marek, Ken" uniqKey="Marek K" first="Ken" last="Marek">Ken Marek</name>
<affiliation>
<nlm:aff id="A24">Institute for Neurodegenerative Disorders, New Haven, CT, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Day Williams, Aaron G" sort="Day Williams, Aaron G" uniqKey="Day Williams A" first="Aaron G." last="Day-Williams">Aaron G. Day-Williams</name>
<affiliation>
<nlm:aff id="A25">Translational Sciences and Technology, Biogen Idec, Cambridge, MA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Stone, David J" sort="Stone, David J" uniqKey="Stone D" first="David J." last="Stone">David J. Stone</name>
<affiliation>
<nlm:aff id="A18">Genetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P. A." last="Ioannidis">John P. A. Ioannidis</name>
<affiliation>
<nlm:aff id="A26">Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A27">Department of Medicine, Stanford Prevention Research Center, Stanford, California, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A28">Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A29">Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, California, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew B." last="Singleton">Andrew B. Singleton</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
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<title xml:lang="en" level="a" type="main">Diagnosis of Parkinson’s disease on the basis of clinical–genetic classification: a population-based modelling study</title>
<author>
<name sortKey="Nalls, Mike A" sort="Nalls, Mike A" uniqKey="Nalls M" first="Mike A." last="Nalls">Mike A. Nalls</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mclean, Cory Y" sort="Mclean, Cory Y" uniqKey="Mclean C" first="Cory Y." last="Mclean">Cory Y. Mclean</name>
<affiliation>
<nlm:aff id="A2">23andMe, Inc., Mountain View, CA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Rick, Jacqueline" sort="Rick, Jacqueline" uniqKey="Rick J" first="Jacqueline" last="Rick">Jacqueline Rick</name>
<affiliation>
<nlm:aff id="A3">Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Eberly, Shirley" sort="Eberly, Shirley" uniqKey="Eberly S" first="Shirley" last="Eberly">Shirley Eberly</name>
<affiliation>
<nlm:aff id="A4">Department of Biostatistics, University of Rochester Medical Center, Rochester, NY, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Hutten, Samantha J" sort="Hutten, Samantha J" uniqKey="Hutten S" first="Samantha J." last="Hutten">Samantha J. Hutten</name>
<affiliation>
<nlm:aff id="A5">The Michael J. Fox Foundation for Parkinson’s Research, New York, NY 10018, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gwinn, Katrina" sort="Gwinn, Katrina" uniqKey="Gwinn K" first="Katrina" last="Gwinn">Katrina Gwinn</name>
<affiliation>
<nlm:aff id="A6">National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sutherland, Margaret" sort="Sutherland, Margaret" uniqKey="Sutherland M" first="Margaret" last="Sutherland">Margaret Sutherland</name>
<affiliation>
<nlm:aff id="A6">National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name>
<affiliation>
<nlm:aff id="A7">INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A8">Paul Sabatier University, Toulouse, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name>
<affiliation>
<nlm:aff id="A9">Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Williams, Nigel" sort="Williams, Nigel" uniqKey="Williams N" first="Nigel" last="Williams">Nigel Williams</name>
<affiliation>
<nlm:aff id="A10">Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name>
<affiliation>
<nlm:aff id="A11">Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name>
<affiliation>
<nlm:aff id="A12">Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name>
<affiliation>
<nlm:aff id="A13">Sorbonne Université, UPMC Univ Paris 06, UM 1127, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A14">Inserm, U 1127, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A15">Cnrs, UMR 7225, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A16">ICM, Paris, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A17">AP-HP, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, F-75013, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Price, T Ryan" sort="Price, T Ryan" uniqKey="Price T" first="T. Ryan" last="Price">T. Ryan Price</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Nicolas, Aude" sort="Nicolas, Aude" uniqKey="Nicolas A" first="Aude" last="Nicolas">Aude Nicolas</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Keller, Margaux F" sort="Keller, Margaux F" uniqKey="Keller M" first="Margaux F." last="Keller">Margaux F. Keller</name>
<affiliation>
<nlm:aff id="A18">Genetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Molony, Cliona" sort="Molony, Cliona" uniqKey="Molony C" first="Cliona" last="Molony">Cliona Molony</name>
<affiliation>
<nlm:aff id="A18">Genetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gibbs, J Raphael" sort="Gibbs, J Raphael" uniqKey="Gibbs J" first="J. Raphael" last="Gibbs">J. Raphael Gibbs</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Chen Plotkin, Alice" sort="Chen Plotkin, Alice" uniqKey="Chen Plotkin A" first="Alice" last="Chen-Plotkin">Alice Chen-Plotkin</name>
<affiliation>
<nlm:aff id="A3">Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Suh, Eunran" sort="Suh, Eunran" uniqKey="Suh E" first="Eunran" last="Suh">Eunran Suh</name>
<affiliation>
<nlm:aff id="A19">Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Letson, Christopher" sort="Letson, Christopher" uniqKey="Letson C" first="Christopher" last="Letson">Christopher Letson</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Fiandaca, Massimo S" sort="Fiandaca, Massimo S" uniqKey="Fiandaca M" first="Massimo S." last="Fiandaca">Massimo S. Fiandaca</name>
<affiliation>
<nlm:aff id="A20">Department of Neurology, Georgetown University Medical Center, DC, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mapstone, Mark" sort="Mapstone, Mark" uniqKey="Mapstone M" first="Mark" last="Mapstone">Mark Mapstone</name>
<affiliation>
<nlm:aff id="A21">Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Federoff, Howard J" sort="Federoff, Howard J" uniqKey="Federoff H" first="Howard J." last="Federoff">Howard J. Federoff</name>
<affiliation>
<nlm:aff id="A20">Department of Neurology, Georgetown University Medical Center, DC, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Noyce, Alastair J" sort="Noyce, Alastair J" uniqKey="Noyce A" first="Alastair J" last="Noyce">Alastair J. Noyce</name>
<affiliation>
<nlm:aff id="A11">Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Morris, Huw" sort="Morris, Huw" uniqKey="Morris H" first="Huw" last="Morris">Huw Morris</name>
<affiliation>
<nlm:aff id="A11">Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Van Deerlin, Vivianna M" sort="Van Deerlin, Vivianna M" uniqKey="Van Deerlin V" first="Vivianna M." last="Van Deerlin">Vivianna M. Van Deerlin</name>
<affiliation>
<nlm:aff id="A19">Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Weintraub, Daniel" sort="Weintraub, Daniel" uniqKey="Weintraub D" first="Daniel" last="Weintraub">Daniel Weintraub</name>
<affiliation>
<nlm:aff id="A3">Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A22">Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Zabetian, Cyrus" sort="Zabetian, Cyrus" uniqKey="Zabetian C" first="Cyrus" last="Zabetian">Cyrus Zabetian</name>
<affiliation>
<nlm:aff id="A23">Department of Neurology; Division of Neurogenetics; Staff Neurologist, VA Puget Sound Health Care System, Seattle, WA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Hernandez, Dena G" sort="Hernandez, Dena G" uniqKey="Hernandez D" first="Dena G." last="Hernandez">Dena G. Hernandez</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name>
<affiliation>
<nlm:aff id="A13">Sorbonne Université, UPMC Univ Paris 06, UM 1127, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A14">Inserm, U 1127, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A15">Cnrs, UMR 7225, ICM, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A16">ICM, Paris, F-75013 Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A17">AP-HP, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, F-75013, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mullins, Meghan" sort="Mullins, Meghan" uniqKey="Mullins M" first="Meghan" last="Mullins">Meghan Mullins</name>
<affiliation>
<nlm:aff id="A2">23andMe, Inc., Mountain View, CA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Conley, Emily Drabant" sort="Conley, Emily Drabant" uniqKey="Conley E" first="Emily Drabant" last="Conley">Emily Drabant Conley</name>
<affiliation>
<nlm:aff id="A2">23andMe, Inc., Mountain View, CA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Northover, Carrie" sort="Northover, Carrie" uniqKey="Northover C" first="Carrie" last="Northover">Carrie Northover</name>
<affiliation>
<nlm:aff id="A2">23andMe, Inc., Mountain View, CA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Frasier, Mark" sort="Frasier, Mark" uniqKey="Frasier M" first="Mark" last="Frasier">Mark Frasier</name>
<affiliation>
<nlm:aff id="A5">The Michael J. Fox Foundation for Parkinson’s Research, New York, NY 10018, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Marek, Ken" sort="Marek, Ken" uniqKey="Marek K" first="Ken" last="Marek">Ken Marek</name>
<affiliation>
<nlm:aff id="A24">Institute for Neurodegenerative Disorders, New Haven, CT, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Day Williams, Aaron G" sort="Day Williams, Aaron G" uniqKey="Day Williams A" first="Aaron G." last="Day-Williams">Aaron G. Day-Williams</name>
<affiliation>
<nlm:aff id="A25">Translational Sciences and Technology, Biogen Idec, Cambridge, MA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Stone, David J" sort="Stone, David J" uniqKey="Stone D" first="David J." last="Stone">David J. Stone</name>
<affiliation>
<nlm:aff id="A18">Genetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P. A." last="Ioannidis">John P. A. Ioannidis</name>
<affiliation>
<nlm:aff id="A26">Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A27">Department of Medicine, Stanford Prevention Research Center, Stanford, California, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A28">Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A29">Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, California, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew B." last="Singleton">Andrew B. Singleton</name>
<affiliation>
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">The Lancet. Neurology</title>
<idno type="ISSN">1474-4422</idno>
<idno type="eISSN">1474-4465</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec id="S1">
<title>Background</title>
<p id="P1">Accurate diagnosis and early detection of complex disease has the potential to be of enormous benefit to clinical trialists, patients, and researchers alike. We sought to create a non-invasive, low-cost, and accurate classification model for diagnosing Parkinson’s disease risk to serve as a basis for future disease prediction studies in prospective longitudinal cohorts.</p>
</sec>
<sec id="S2">
<title>Methods</title>
<p id="P2">We developed a simple disease classifying model within 367 patients with Parkinson’s disease and phenotypically typical imaging data and 165 controls without neurological disease of the Parkinson’s Progression Marker Initiative (PPMI) study. Olfactory function, genetic risk, family history of PD, age and gender were algorithmically selected as significant contributors to our classifying model. This model was developed using the PPMI study then tested in 825 patients with Parkinson’s disease and 261 controls from five independent studies with varying recruitment strategies and designs including the Parkinson’s Disease Biomarkers Program (PDBP), Parkinson’s Associated Risk Study (PARS), 23andMe, Longitudinal and Biomarker Study in PD (LABS-PD), and Morris K. Udall Parkinson’s Disease Research Center of Excellence (Penn-Udall).</p>
</sec>
<sec id="S3">
<title>Findings</title>
<p id="P3">Our initial model correctly distinguished patients with Parkinson’s disease from controls at an area under the curve (AUC) of 0.923 (95% CI = 0.900 – 0.946) with high sensitivity (0.834, 95% CI = 0.711 – 0.883) and specificity (0.903, 95% CI = 0.824 – 0.946) in PPMI at its optimal AUC threshold (0.655). The model is also well-calibrated with all Hosmer-Lemeshow simulations suggesting that when parsed into random subgroups, the actual data mirrors that of the larger expected data, demonstrating that our model is robust and fits well. Likewise external validation shows excellent classification of PD with AUCs of 0.894 in PDBP, 0.998 in PARS, 0.955 in 23andMe, 0.929 in LABS-PD, and 0.939 in Penn-Udall. Additionally, when our model classifies SWEDD as PD, they convert within one year to typical PD more than would be expected by chance, with 4 out of 17 classified as PD converting to PD during brief follow-up; while SWEDD not classified as PD showed one conversion to PD out of 38 participants (test of proportions, p-value = 0.003).</p>
</sec>
<sec id="S4">
<title>Interpretation</title>
<p id="P4">This model may serve as a basis for future investigations into the classification, prediction and treatment of Parkinson’s disease, particularly those planning on attempting to identify prodromal or preclinical etiologically typical PD cases in prospective cohorts for efficient interventional and biomarker studies.</p>
</sec>
<sec id="S5">
<title>Funding</title>
<p id="P5">Please see the acknowledgements and funding section at the end of the manuscript.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">101139309</journal-id>
<journal-id journal-id-type="pubmed-jr-id">30413</journal-id>
<journal-id journal-id-type="nlm-ta">Lancet Neurol</journal-id>
<journal-id journal-id-type="iso-abbrev">Lancet Neurol</journal-id>
<journal-title-group>
<journal-title>The Lancet. Neurology</journal-title>
</journal-title-group>
<issn pub-type="ppub">1474-4422</issn>
<issn pub-type="epub">1474-4465</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">26271532</article-id>
<article-id pub-id-type="pmc">4575273</article-id>
<article-id pub-id-type="doi">10.1016/S1474-4422(15)00178-7</article-id>
<article-id pub-id-type="manuscript">NIHMS715938</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Diagnosis of Parkinson’s disease on the basis of clinical–genetic classification: a population-based modelling study</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Nalls</surname>
<given-names>Mike A.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>McLean</surname>
<given-names>Cory Y.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rick</surname>
<given-names>Jacqueline</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Eberly</surname>
<given-names>Shirley</given-names>
</name>
<degrees>MS</degrees>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hutten</surname>
<given-names>Samantha J.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gwinn</surname>
<given-names>Katrina</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sutherland</surname>
<given-names>Margaret</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Martinez</surname>
<given-names>Maria</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A7">7</xref>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Heutink</surname>
<given-names>Peter</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Williams</surname>
<given-names>Nigel</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hardy</surname>
<given-names>John</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gasser</surname>
<given-names>Thomas</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Brice</surname>
<given-names>Alexis</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A13">13</xref>
<xref ref-type="aff" rid="A14">14</xref>
<xref ref-type="aff" rid="A15">15</xref>
<xref ref-type="aff" rid="A16">16</xref>
<xref ref-type="aff" rid="A17">17</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Price</surname>
<given-names>T. Ryan</given-names>
</name>
<degrees>MS</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nicolas</surname>
<given-names>Aude</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Keller</surname>
<given-names>Margaux F.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Molony</surname>
<given-names>Cliona</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gibbs</surname>
<given-names>J. Raphael</given-names>
</name>
<degrees>MS</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen-Plotkin</surname>
<given-names>Alice</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Suh</surname>
<given-names>Eunran</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Letson</surname>
<given-names>Christopher</given-names>
</name>
<degrees>BS</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fiandaca</surname>
<given-names>Massimo S.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A20">20</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mapstone</surname>
<given-names>Mark</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Federoff</surname>
<given-names>Howard J.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A20">20</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Noyce</surname>
<given-names>Alastair J</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Morris</surname>
<given-names>Huw</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Van Deerlin</surname>
<given-names>Vivianna M.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Weintraub</surname>
<given-names>Daniel</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A22">22</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zabetian</surname>
<given-names>Cyrus</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A23">23</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hernandez</surname>
<given-names>Dena G.</given-names>
</name>
<degrees>MS</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lesage</surname>
<given-names>Suzanne</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A13">13</xref>
<xref ref-type="aff" rid="A14">14</xref>
<xref ref-type="aff" rid="A15">15</xref>
<xref ref-type="aff" rid="A16">16</xref>
<xref ref-type="aff" rid="A17">17</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mullins</surname>
<given-names>Meghan</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Conley</surname>
<given-names>Emily Drabant</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Northover</surname>
<given-names>Carrie</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Frasier</surname>
<given-names>Mark</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Marek</surname>
<given-names>Ken</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A24">24</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Day-Williams</surname>
<given-names>Aaron G.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A25">25</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Stone</surname>
<given-names>David J.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ioannidis</surname>
<given-names>John P. A.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A26">26</xref>
<xref ref-type="aff" rid="A27">27</xref>
<xref ref-type="aff" rid="A28">28</xref>
<xref ref-type="aff" rid="A29">29</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Singleton</surname>
<given-names>Andrew B.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
<on-behalf-of>on behalf of the Parkinson’s Disease Biomarkers Program (PDBP) and the Parkinson’s Progression Marker Initiative (PPMI) investigators</on-behalf-of>
<xref rid="FN2" ref-type="author-notes">$</xref>
</contrib-group>
<aff id="A1">
<label>1</label>
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA</aff>
<aff id="A2">
<label>2</label>
23andMe, Inc., Mountain View, CA, USA</aff>
<aff id="A3">
<label>3</label>
Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</aff>
<aff id="A4">
<label>4</label>
Department of Biostatistics, University of Rochester Medical Center, Rochester, NY, USA</aff>
<aff id="A5">
<label>5</label>
The Michael J. Fox Foundation for Parkinson’s Research, New York, NY 10018, USA</aff>
<aff id="A6">
<label>6</label>
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA</aff>
<aff id="A7">
<label>7</label>
INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France</aff>
<aff id="A8">
<label>8</label>
Paul Sabatier University, Toulouse, France</aff>
<aff id="A9">
<label>9</label>
Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany</aff>
<aff id="A10">
<label>10</label>
Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales</aff>
<aff id="A11">
<label>11</label>
Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK</aff>
<aff id="A12">
<label>12</label>
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany</aff>
<aff id="A13">
<label>13</label>
Sorbonne Université, UPMC Univ Paris 06, UM 1127, ICM, F-75013 Paris, France</aff>
<aff id="A14">
<label>14</label>
Inserm, U 1127, ICM, F-75013 Paris, France</aff>
<aff id="A15">
<label>15</label>
Cnrs, UMR 7225, ICM, F-75013 Paris, France</aff>
<aff id="A16">
<label>16</label>
ICM, Paris, F-75013 Paris, France</aff>
<aff id="A17">
<label>17</label>
AP-HP, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, F-75013, Paris, France</aff>
<aff id="A18">
<label>18</label>
Genetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA</aff>
<aff id="A19">
<label>19</label>
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</aff>
<aff id="A20">
<label>20</label>
Department of Neurology, Georgetown University Medical Center, DC, USA</aff>
<aff id="A21">
<label>21</label>
Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA</aff>
<aff id="A22">
<label>22</label>
Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</aff>
<aff id="A23">
<label>23</label>
Department of Neurology; Division of Neurogenetics; Staff Neurologist, VA Puget Sound Health Care System, Seattle, WA, USA</aff>
<aff id="A24">
<label>24</label>
Institute for Neurodegenerative Disorders, New Haven, CT, USA</aff>
<aff id="A25">
<label>25</label>
Translational Sciences and Technology, Biogen Idec, Cambridge, MA, USA</aff>
<aff id="A26">
<label>26</label>
Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA</aff>
<aff id="A27">
<label>27</label>
Department of Medicine, Stanford Prevention Research Center, Stanford, California, USA</aff>
<aff id="A28">
<label>28</label>
Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA</aff>
<aff id="A29">
<label>29</label>
Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, California, USA</aff>
<author-notes>
<corresp id="FN1">
<label>*</label>
Correspondence: Andrew B. Singleton
<email>singleta@mail.nih.gov</email>
</corresp>
<fn id="FN2">
<label>$</label>
<p>Please see
<xref rid="SD1" ref-type="supplementary-material">supplemental materials</xref>
for an index of PDBP and PPMI investigators and their affiliations</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>16</day>
<month>8</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub">
<day>10</day>
<month>8</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="ppub">
<month>10</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>01</day>
<month>10</month>
<year>2016</year>
</pub-date>
<volume>14</volume>
<issue>10</issue>
<fpage>1002</fpage>
<lpage>1009</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/S1474-4422(15)00178-7</pmc-comment>
<abstract>
<sec id="S1">
<title>Background</title>
<p id="P1">Accurate diagnosis and early detection of complex disease has the potential to be of enormous benefit to clinical trialists, patients, and researchers alike. We sought to create a non-invasive, low-cost, and accurate classification model for diagnosing Parkinson’s disease risk to serve as a basis for future disease prediction studies in prospective longitudinal cohorts.</p>
</sec>
<sec id="S2">
<title>Methods</title>
<p id="P2">We developed a simple disease classifying model within 367 patients with Parkinson’s disease and phenotypically typical imaging data and 165 controls without neurological disease of the Parkinson’s Progression Marker Initiative (PPMI) study. Olfactory function, genetic risk, family history of PD, age and gender were algorithmically selected as significant contributors to our classifying model. This model was developed using the PPMI study then tested in 825 patients with Parkinson’s disease and 261 controls from five independent studies with varying recruitment strategies and designs including the Parkinson’s Disease Biomarkers Program (PDBP), Parkinson’s Associated Risk Study (PARS), 23andMe, Longitudinal and Biomarker Study in PD (LABS-PD), and Morris K. Udall Parkinson’s Disease Research Center of Excellence (Penn-Udall).</p>
</sec>
<sec id="S3">
<title>Findings</title>
<p id="P3">Our initial model correctly distinguished patients with Parkinson’s disease from controls at an area under the curve (AUC) of 0.923 (95% CI = 0.900 – 0.946) with high sensitivity (0.834, 95% CI = 0.711 – 0.883) and specificity (0.903, 95% CI = 0.824 – 0.946) in PPMI at its optimal AUC threshold (0.655). The model is also well-calibrated with all Hosmer-Lemeshow simulations suggesting that when parsed into random subgroups, the actual data mirrors that of the larger expected data, demonstrating that our model is robust and fits well. Likewise external validation shows excellent classification of PD with AUCs of 0.894 in PDBP, 0.998 in PARS, 0.955 in 23andMe, 0.929 in LABS-PD, and 0.939 in Penn-Udall. Additionally, when our model classifies SWEDD as PD, they convert within one year to typical PD more than would be expected by chance, with 4 out of 17 classified as PD converting to PD during brief follow-up; while SWEDD not classified as PD showed one conversion to PD out of 38 participants (test of proportions, p-value = 0.003).</p>
</sec>
<sec id="S4">
<title>Interpretation</title>
<p id="P4">This model may serve as a basis for future investigations into the classification, prediction and treatment of Parkinson’s disease, particularly those planning on attempting to identify prodromal or preclinical etiologically typical PD cases in prospective cohorts for efficient interventional and biomarker studies.</p>
</sec>
<sec id="S5">
<title>Funding</title>
<p id="P5">Please see the acknowledgements and funding section at the end of the manuscript.</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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