The Parkinson's Disease Mendelian Randomization Research Portal

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. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Missing heritability in Parkinson’s disease: the emerging role of non-coding genetic variation

“…Through the integration of tissue-specific DNA methylation and gene expression profiles polygenic risk to PD can be compared to the polygenic risk of another exposure (Nalls et al 2019;Kolber and Krüger 2019). The recently published MR portal allows to browse two-sample MR results from a wide range of exposures with the latest PD Meta-GWAS analysis (Noyce et al 2019).…”

Ten Years of the International Parkinson Disease Genomics Consortium: Progress and Next Steps

“…Using this method it is possible to test whether a trait is causally associated with PD. MR has become increasingly popular over the last few years, in large part due to the growing amount of robust genetic association results and data [13].…”

“…Another important role the IPDGC has, is providing the research community with easy access result summaries that are usable and understandable to basic researchers, such as results from GWAS summary stats, from the MR studies [13] (https://pdgenetics.shinyapps.io/MRportal/) and PD progression studies [17] (https://pdgenetics. shinyapps.io/pdprogmetagwasbrowser/).…”

Causal Association between Periodontitis and Parkinson's Disease: A Bidirectional Mendelian Randomization Study

“…Parkinson's disease (PD) is a neurodegenerative condition with heterogeneous clinical patterns and progression [1,2]. Despite the cause of PD is still to be fully understood, a comprehensive mendelian randomization (MR) study described the relative risk of developing PD for 12 different exposures [3]. Furthermore, the role of inflammation in PD, either by local or systemic causes, has been consistently researched [4].…”