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Research Article

Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database

  • Christina M. Lill,

    Affiliations: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America, Department of Neurology, Medical Center of the Johannes Gutenberg-University, Mainz, Germany, Department of Neurology, University Hospital, Münster, Germany

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  • Johannes T. Roehr,

    Affiliations: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany, Department of Mathematics and Computer Science, Free University, Berlin, Germany

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  • Matthew B. McQueen,

    Affiliation: Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado, United States of America

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  • Fotini K. Kavvoura,

    Affiliations: Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece, Centre for Diabetes and Endocrinology, Royal Berkshire Hospital, Reading, United Kingdom, Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, University of Oxford, Oxford, United Kingdom

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  • Sachin Bagade,

    Affiliation: Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America

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  • Brit-Maren M. Schjeide,

    Affiliation: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany

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  • Leif M. Schjeide,

    Affiliation: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany

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  • Esther Meissner,

    Affiliation: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany

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  • Ute Zauft,

    Affiliation: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany

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  • Nicole C. Allen,

    Affiliation: Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America

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  • Tian Liu,

    Affiliations: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany, Max Planck Institute for Human Development, Berlin, Germany

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  • Marcel Schilling,

    Affiliations: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany, Department of Mathematics and Computer Science, Free University, Berlin, Germany

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  • Kari J. Anderson,

    Affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America

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  • Gary Beecham,

    Affiliation: John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, United States of America

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  • Daniela Berg,

    Affiliations: Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany, DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany

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  • Joanna M. Biernacka,

    Affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America

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  • Alexis Brice,

    Affiliations: INSERM, UMR_S975, Paris, France, Université Pierre et Marie Curie-Paris, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UMR-S975, Paris, France, CNRS, UMR 7225, Paris, France, AP-HP, Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris, France

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  • Anita L. DeStefano,

    Affiliations: Department of Neurology, Boston University School of Medicine, Boston University, Boston, Massachusetts, United States of America, Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America

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  • Chuong B. Do,

    Affiliation: 23andMe, Mountain View, California, United States of America

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  • Nicholas Eriksson,

    Affiliation: 23andMe, Mountain View, California, United States of America

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  • Stewart A. Factor,

    Affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, United States of America

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  • Matthew J. Farrer,

    Affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada

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  • Tatiana Foroud,

    Affiliation: Indiana University School of Medicine, Indianapolis, Indiana, United States of America

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  • Thomas Gasser,

    Affiliations: Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany, DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany

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  • Taye Hamza,

    Affiliation: New York State Department of Health Wadsworth Center, Albany, New York, United States of America

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  • John A. Hardy,

    Affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, United Kingdom

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  • Peter Heutink,

    Affiliation: Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, The Netherlands

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  • Erin M. Hill-Burns,

    Affiliation: New York State Department of Health Wadsworth Center, Albany, New York, United States of America

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  • Christine Klein,

    Affiliation: Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lübeck, Lübeck, Germany

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  • Jeanne C. Latourelle,

    Affiliation: Department of Neurology, Boston University School of Medicine, Boston University, Boston, Massachusetts, United States of America

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  • Demetrius M. Maraganore,

    Affiliation: Department of Neurology, NorthShore University Health System, Evanston, Illinois, United States of America

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  • Eden R. Martin,

    Affiliation: John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, United States of America

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  • Maria Martinez,

    Affiliations: INSERM UMR 1043, CPTP, Toulouse, France, Paul Sabatier University, Toulouse, France

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  • Richard H. Myers,

    Affiliation: Department of Neurology, Boston University School of Medicine, Boston University, Boston, Massachusetts, United States of America

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  • Michael A. Nalls,

    Affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America

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  • Nathan Pankratz,

    Affiliation: Indiana University School of Medicine, Indianapolis, Indiana, United States of America

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  • Haydeh Payami,

    Affiliation: New York State Department of Health Wadsworth Center, Albany, New York, United States of America

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  • Wataru Satake,

    Affiliation: Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan

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  • William K. Scott,

    Affiliation: John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, United States of America

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  • Manu Sharma,

    Affiliations: Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany, DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany

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  • Andrew B. Singleton,

    Affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America

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  • Kari Stefansson,

    Affiliation: deCODE genetics, Reykjavik, Iceland

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  • Tatsushi Toda,

    Affiliation: Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan

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  • Joyce Y. Tung,

    Affiliation: 23andMe, Mountain View, California, United States of America

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  • Jeffery Vance,

    Affiliation: John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, United States of America

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  • Nick W. Wood,

    Affiliations: UCL Genetics Institute, University College London, London, United Kingdom, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, United Kingdom

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  • Cyrus P. Zabetian,

    Affiliation: VA Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, Washington, United States of America

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  • 23andMe, The Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium ,

    Memberships of the consortia are provided in Text S1.

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  • The International Parkinson's Disease Genomics Consortium (IPDGC) ,

    Memberships of the consortia are provided in Text S1.

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  • The Parkinson's Disease GWAS Consortium ,

    Memberships of the consortia are provided in Text S1.

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  • The Wellcome Trust Case Control Consortium 2 (WTCCC2) ,

    Memberships of the consortia are provided in Text S1.

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  • Peter Young,

    Affiliation: Department of Neurology, University Hospital, Münster, Germany

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  • Rudolph E. Tanzi,

    Affiliation: Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America

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  • Muin J. Khoury,

    Affiliation: Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

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  • Frauke Zipp,

    Affiliation: Department of Neurology, Medical Center of the Johannes Gutenberg-University, Mainz, Germany

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  • Hans Lehrach,

    Affiliation: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany

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  • John P. A. Ioannidis,

    Affiliations: Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece, Biomedical Research Institute, Foundation for Research and Technology–Hellas, Ioannina, Greece, Center for Genetic Epidemiology and Modeling and Tufts Clinical and Translational Science Institute, Tufts University School of Medicine, Boston, Massachusetts, United States of America, Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, United States of America

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  • Lars Bertram mail

    lbertram@molgen.mpg.de

    Affiliations: Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America

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  • Published: March 15, 2012
  • DOI: 10.1371/journal.pgen.1002548

About the Authors

Christina M. Lill, Johannes T. Roehr, Brit-Maren M. Schjeide, Leif M. Schjeide, Esther Meissner, Ute Zauft, Tian Liu, Marcel Schilling, Hans Lehrach, Lars Bertram
Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
Christina M. Lill, Sachin Bagade, Nicole C. Allen, Rudolph E. Tanzi, Lars Bertram
Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America
Christina M. Lill, Frauke Zipp
Department of Neurology, Medical Center of the Johannes Gutenberg-University, Mainz, Germany
Christina M. Lill, Peter Young
Department of Neurology, University Hospital, Münster, Germany
Johannes T. Roehr, Marcel Schilling
Department of Mathematics and Computer Science, Free University, Berlin, Germany
Matthew B. McQueen
Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado, United States of America
Fotini K. Kavvoura, John P. A. Ioannidis
Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
Fotini K. Kavvoura
Centre for Diabetes and Endocrinology, Royal Berkshire Hospital, Reading, United Kingdom
Fotini K. Kavvoura
Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, University of Oxford, Oxford, United Kingdom
Tian Liu
Max Planck Institute for Human Development, Berlin, Germany
Kari J. Anderson, Joanna M. Biernacka
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America
Gary Beecham, Eden R. Martin, William K. Scott, Jeffery Vance
John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, United States of America
Daniela Berg, Thomas Gasser, Manu Sharma
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Daniela Berg, Thomas Gasser, Manu Sharma
DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany
Alexis Brice
INSERM, UMR_S975, Paris, France
Alexis Brice
Université Pierre et Marie Curie-Paris, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UMR-S975, Paris, France
Alexis Brice
CNRS, UMR 7225, Paris, France
Alexis Brice
AP-HP, Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris, France
Anita L. DeStefano, Jeanne C. Latourelle, Richard H. Myers
Department of Neurology, Boston University School of Medicine, Boston University, Boston, Massachusetts, United States of America
Anita L. DeStefano
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America
Chuong B. Do, Nicholas Eriksson, Joyce Y. Tung
23andMe, Mountain View, California, United States of America
Stewart A. Factor
Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, United States of America
Matthew J. Farrer
Department of Medical Genetics, University of British Columbia, Vancouver, Canada
Tatiana Foroud, Nathan Pankratz
Indiana University School of Medicine, Indianapolis, Indiana, United States of America
Taye Hamza, Erin M. Hill-Burns, Haydeh Payami
New York State Department of Health Wadsworth Center, Albany, New York, United States of America
John A. Hardy, Nick W. Wood
Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, United Kingdom
Peter Heutink
Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, The Netherlands
Christine Klein
Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lübeck, Lübeck, Germany
Demetrius M. Maraganore
Department of Neurology, NorthShore University Health System, Evanston, Illinois, United States of America
Maria Martinez
INSERM UMR 1043, CPTP, Toulouse, France
Maria Martinez
Paul Sabatier University, Toulouse, France
Michael A. Nalls, Andrew B. Singleton
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America
Wataru Satake, Tatsushi Toda
Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan
Kari Stefansson
deCODE genetics, Reykjavik, Iceland
Nick W. Wood
UCL Genetics Institute, University College London, London, United Kingdom
Cyrus P. Zabetian
VA Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, Washington, United States of America
Muin J. Khoury
Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
John P. A. Ioannidis
Biomedical Research Institute, Foundation for Research and Technology–Hellas, Ioannina, Greece
John P. A. Ioannidis
Center for Genetic Epidemiology and Modeling and Tufts Clinical and Translational Science Institute, Tufts University School of Medicine, Boston, Massachusetts, United States of America
John P. A. Ioannidis
Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, United States of America

Corresponding Author

Email: lbertram@molgen.mpg.de

Competing Interests

CB Do, N Eriksson, and JY Tung are employed by 23andMe and own stock options in the company. MJ Farrer and Mayo Foundation received royalties from H.Lundbeck A/S and Isis Pharmaceuticals. In addition, MJ Farrer has received an honorarium for a seminar at Genzyme. T Gasser has received consultancy fees from Cephalon and Merck-Serono, grants from Novartis, payments for lectures including service on speakers' bureaus from Boehringer Ingelheim, Merck-Serono, UCB, and Valean, and holds patents NGFN2 and KASPP. JA Hardy has received consulting fees or honoraria from Eisai and his institute has received consulting fees or honoraria from Merck-Serono. DM Maraganore has received extramural research funding support from the National Institutes of Health (2R01 ES10751), the Michael J. Fox Foundation (Linked Efforts to Accelerate Parkinson Solutions Award, Edmond J. Safra Global Genetics Consortia Award), and from Alnylam Pharmaceuticals and Medtronic (observational studies of Parkinson's disease). DM Maraganore has also received intramural research funding support from the Mayo Clinic and from NorthShore University Health System. DM Maraganore filed a provisional patent for a method to predict Parkinson's disease. This provisional patent is unlicensed. He also filed a provisional patent for a method to treat neurodegenerative disorders. That provisional patent has been licensed to Alnylam Pharmaceuticals and DM Maraganore has received royalty payments in total of less than $20,000. K Stefansson has received grants from deCODE.

Author Contributions

Conceived and designed the experiments: CM Lill, MB McQueen, JPA Ioannidis, L Bertram. Performed the experiments: CM Lill, JT Roehr, S Bagade, B-M Schjeide, E Meissner, U Zauft, NC Allen, KJ Anderson, G Beecham, D Berg, JM Biernacka, A Brice, AL DeStefano, CB Do, N Eriksson, SA Factor, MJ Farrer, T Foroud, T Gasser, T Hamza, JA Hardy, P Heutink, C Klein, JC Latourelle, DM Maraganore, ER Martin, M Martinez, RH Myers, H Payami, WK Scott, M Sharma, AB Singleton, K Stefansson, T Toda, JY Tung, J Vance, NW Wood, CP Zabetian, 23andMe, GEO-PD, IPDGC, Parkinson's Disease GWAS, WTCC2. Analyzed the data: CM Lill, JT Roehr, MB McQueen, FK Kavvoura, L Bertram. Wrote the paper: CM Lill, JPA Ioannidis, L Bertram. Helped write the manuscript: E Meissner, MJ Farrer, T Foroud, T Gasser, C Klein, DM Maraganore, H Payami, AB Singleton, M Sharma, F Zipp, H Lehrach. Helped analyze the data: S Bagade, T Liu, M Schilling, CB Do, N Eriksson, T Hamza, EM Hill-Burns, MA Nalls, N Pankratz, W Satake, M Sharma. Interpretation of results: CM Lill, JPA Ioannidis, L Bertram. Study coordination: CM Lill, T Foroud, JA Hardy, H Payami, AB Singleton, P Young, RE Tanzi, MJ Khoury, F Zipp, H Lehrach, JPA Ioannidis, L Bertram. Literature searches and data entry: CM Lill, S Bagade, B-M Schjeide, E Meissner, U Zauft, N Allen.