Milestones in PD genetics

Authors

  • Thomas Gasser MD,

    Corresponding author
    1. Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, and German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
    • Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases and German Center for Neurodegenerative Diseases (DZNE), Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany
    Search for more papers by this author
  • John Hardy PhD,

    1. Reta Lilla Weston Laboratories and Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
    Search for more papers by this author
  • Yoshikuni Mizuno MD

    1. Department of Neuro-regenerative Medicine, Kitasato University School of Medicine, Kanagawa, Japan
    Search for more papers by this author

  • Relevant conflict of interest/financial disclosures: Nothing to report.

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Over the last 25 years, genetic findings have profoundly changed our views on the etiology of Parkinson's disease. Linkage studies and positional cloning strategies have identified mutations in a number of genes that cause several monogenic autosomal-dominant or autosomal-recessive forms of the disorder. Although most of these Mendelian forms of Parkinson's disease are rare, whole-genome association studies have more recently provided convincing evidence that low-penetrance variants in at least some of these, but also in several other genes, play a direct role in the etiology of the common sporadic disease as well. In addition, rare variants with intermediate-effect strengths in genes such as Gaucher's disease–associated glucocerebrosidase A have been discovered as important risk factors. “Next-generation” sequencing technologies are expected by some to identify many more of these variants. Thus, an increasingly complex network of genes contributing in different ways to disease risk and progression is emerging. These findings may provide the “genetic entry points” to identify molecular targets and readouts necessary to design rational disease-modifying treatments. © 2011 Movement Disorder Society

Ancillary