The Parkinson’s Disease Mendelian Randomization Research Portal

Alastair J. Noyce, Sara Bandres-Ciga, Jonggeol Kim, Karl Helibron, Demis A. Kia, Gibran Hemani, Angil Xue, Debbie A Lawlor, George Davey Smith, Raquel Duran, Ziv Gan-Or, Cornelis Blauwendraat, J Raphael Gibbs, David A. Hinds, Jian Yang, Peter M Visscher, Jack Cuzick, Huw Morris, John Hardy, Nicholas WoodMike A Nalls, Andrew B Singleton, International Parkinson's Disease Genomics Consortium (IPDGC), the 23 and Me Research Team

Research output: Contribution to journalArticle (Academic Journal)peer-review

41 Citations (Scopus)
128 Downloads (Pure)

Abstract

Background
Mendelian randomization is a method for exploring observational associations to find evidence of causality.

Objective
To apply Mendelian randomization between risk factors/phenotypic traits (exposures) and Parkinson’s disease in a large, unbiased manner, and to create a public resource for research.

Methods
We used two-sample Mendelian randomization in which the summary statistics relating to single nucleotide polymorphisms from 5,839 genome wide association studies of exposures were used to assess causal relationships with Parkinson’s disease. We selected the highest quality exposure genome wide association studies for this report (n=401). For the disease outcome, summary statistics from the largest published Parkinson’s disease genome wide association studies were used. For each exposure, the causal effect on Parkinson’s disease was assessed using the inverse variance weighted method, followed by a range of sensitivity analyses. We used a false discovery rate of 5% from the inverse variance weighted analysis to prioritize exposures of interest.

Results
We observed evidence for causal associations between twelve exposures and risk of Parkinson’s disease. Of these, nine were effects related to increasing adiposity and decreasing risk of Parkinson’s disease. The remaining top three exposures that affected Parkinson’s disease risk were tea drinking, time spent watching television and forced vital capacity, but these may have been biased and were less convincing. Other exposures at nominal statistical significance included inverse effects of smoking and alcohol.

Discussion
We present a new platform which offers Mendelian randomization analyses for a total of 5,839 genome wide association studies versus the largest Parkinson’s disease genome wide association studies available (https://pdgenetics.shinyapps.io/pdgenetics/). Alongside, we report further evidence to support a causal role for adiposity on lowering the risk of Parkinson’s disease.
Original languageEnglish
Pages (from-to)1864 - 1872
Number of pages9
JournalMovement Disorders
Volume34
Issue number12
Early online date28 Oct 2019
DOIs
Publication statusPublished - 17 Dec 2019

Keywords

  • public resource
  • risk factor
  • Parkinson’s disease
  • Mendelian randomization

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