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The Parkinson's Disease Genome‐Wide Association Study Locus Browser

Grenn, Francis P., Kim, Jonggeol J., Makarious, Mary B., Iwaki, Hirotaka, Illarionova, Anastasia, Brolin, Kajsa, Kluss, Jillian H., Schumacher‐Schuh, Artur F. +18 more·2020·Movement Disorders
DOI 10.1002/mds.28197PMC PMC7754106

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Abstract

Background: Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome‐wide association studies. The most recent large‐scale PD genome‐wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the causal gene(s) and variant(s) at each genome‐wide association study locus. The objective of the current study was to create a tool that would display data for relevant PD risk loci and provide guidance with the prioritization of causal genes and potential mechanisms at each locus. Methods: We included all significant genome‐wide signals from multiple recent PD genome‐wide association studies including themost recent PD risk genome‐wide association study, age‐at‐onset genome‐wide association study, progression genome‐wide association study, and Asian population PD risk genome‐wide association study. We gathered data for all genes 1 Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self‐ranked criteria. Multiple databases were queried for each gene to collect additional causal data. Results: We created a PD genome‐wide association study browser tool ( https://pdgenetics.shinyapps.io/GWASBrowser/ ) to assist the PD research community with the prioritization of genes for follow‐up functional studies to identify potential therapeutic targets. Conclusions: Our PD genome‐wide association study browser tool provides users with a useful method of identifying potential causal genes at all known PD risk loci from large‐scale PD genome‐wide association studies. We plan to update this tool with new relevant data as sample sizes increase and new PD risk loci are discovered. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

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Cited by

Sorted by citations

Authors
Grenn, F. P., Kim, J. J., Makarious, M. B., Iwaki, H., Illarionova, A., Brolin, K., Kluss, J. H., Schumacher‐Schuh, A. F., Leonard, H., Faghri, F., Billingsley, K., Krohn, L., Hall, A., Diez‐Fairen, M., Periñán, M. T., Foo, J. N., Sandor, C., Webber, C., Fiske, B. K., Gibbs, J. R., Nalls, M. A., Singleton, A. B., Bandres‐Ciga, S., Reed, X., Blauwendraat, C., & the International Parkinson's Disease Genomics Consortium (IPDGC)
Affiliations
  • Laboratory of Neurogenetics National Institute on Aging, National Institutes of Health Bethesda Maryland USA
  • German Center for Neurodegenerative Diseases Tubingen Germany
  • Lund University Translational Neurogenetics Unit, Department of Experimental Medical Science Lund Sweden
  • Universidade Federal do Rio Grande do Sul Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
  • Department of Human Genetics McGill University Montreal Quebec Canada
  • Department of Molecular and Clinical Pharmacology Institute of Translational Medicine, University of Liverpool Liverpool UK
  • Fundació Docència i Recerca Mútua Terrassa and Movement Disorders Unit, Department of Neurology University Hospital Mútua Terrassa Barcelona Spain
  • Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla Seville Spain
  • Lee Kong Chian School of Medicine Nanyang Technological University Singapore Singapore Singapore
  • UK Dementia Research Institute, Cardiff University Cardiff UK
  • The Michael J. Fox Foundation for Parkinson's Research, Grand Central Station New York NY USA
Venue
Movement Disorders
Publisher
Wiley
Published
2020-08-31
Volume
35
Issue
11
Pages
2056-2067
ISSN
  • 0885-3185
  • 1531-8257
DOI
10.1002/mds.28197
PMC
PMC7754106
Cited by
103
References
6
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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