Noyce, AJ;
Bandres-Ciga, S;
Kim, J;
Heilbron, K;
Kia, D;
Hemani, G;
Xue, A;
... Singleton, AB; + view all
(2019)
The Parkinson's Disease Mendelian Randomization Research Portal.
Movement Disorders
10.1002/mds.27873.
(In press).
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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 PD 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 PD. 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 PD genome‐wide association studies were used. For each exposure, the causal effect on PD 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 12 exposures and risk of PD. Of these, nine were effects related to increasing adiposity and decreasing risk of PD. The remaining top three exposures that affected PD 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. Conclusions We present a new platform which offers Mendelian randomization analyses for a total of 5,839 genome‐wide association studies versus the largest PD genome‐wide association studies available (https://pdgenetics.shinyapps.io/MRportal/). Alongside, we report further evidence to support a causal role for adiposity on lowering the risk of PD
| Type: | Article |
|---|---|
| Title: | The Parkinson's Disease Mendelian Randomization Research Portal |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/mds.27873 |
| Publisher version: | https://doi.org/10.1002/mds.27873 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Mendelian randomization, Parkinson's disease, public resource, risk factor |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10084681 |
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