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 Wood; Mike A Nalls; Andrew B Singleton; International Parkinson's Disease Genomics Consortium (IPDGC); the 23 and Me Research Team

doi:10.1002/mds.27873

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 journal › Article (Academic Journal) › peer-review

34 Citations (Scopus)

93 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 language	English
Pages (from-to)	1864 - 1872
Number of pages	9
Journal	Movement Disorders
Volume	34
Issue number	12
Early online date	28 Oct 2019
DOIs	https://doi.org/10.1002/mds.27873
Publication status	Published - 17 Dec 2019

Keywords

public resource
risk factor
Parkinson’s disease
Mendelian randomization

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10.1002/mds.27873

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8073 MRC IEU - Programme 6
Lawlor, D. A.
1/04/18 → 31/03/23
Project: Research
IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. & Davey Smith, G.
1/04/18 → 31/03/23
Project: Research
NIHR BRC Translational Population Health
Davey Smith, G.
1/04/17 → 31/03/22
Project: Research, Parent

Cite this

Noyce, A. J., Bandres-Ciga, S., Kim, J., Helibron, K., Kia, D. A., Hemani, G., Xue, A., Lawlor, D. A., Davey Smith, G., Duran, R., Gan-Or, Z., Blauwendraat, C., Gibbs, J. R., Hinds, D. A., Yang, J., Visscher, P. M., Cuzick, J., Morris, H., Hardy, J., ... the 23 and Me Research Team (2019). The Parkinson’s Disease Mendelian Randomization Research Portal. Movement Disorders, 34(12), 1864 - 1872. https://doi.org/10.1002/mds.27873

@article{82b58bc0f20643ba876b373474a22398,

title = "The Parkinson{\textquoteright}s Disease Mendelian Randomization Research Portal",

abstract = "BackgroundMendelian randomization is a method for exploring observational associations to find evidence of causality. ObjectiveTo apply Mendelian randomization between risk factors/phenotypic traits (exposures) and Parkinson{\textquoteright}s disease in a large, unbiased manner, and to create a public resource for research.MethodsWe 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{\textquoteright}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{\textquoteright}s disease genome wide association studies were used. For each exposure, the causal effect on Parkinson{\textquoteright}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. ResultsWe observed evidence for causal associations between twelve exposures and risk of Parkinson{\textquoteright}s disease. Of these, nine were effects related to increasing adiposity and decreasing risk of Parkinson{\textquoteright}s disease. The remaining top three exposures that affected Parkinson{\textquoteright}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.DiscussionWe present a new platform which offers Mendelian randomization analyses for a total of 5,839 genome wide association studies versus the largest Parkinson{\textquoteright}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{\textquoteright}s disease.",

keywords = "public resource, risk factor, Parkinson{\textquoteright}s disease, Mendelian randomization",

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

year = "2019",

month = dec,

day = "17",

doi = "10.1002/mds.27873",

language = "English",

volume = "34",

pages = "1864 -- 1872",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "Wiley",

number = "12",

}

Noyce, AJ, Bandres-Ciga, S, Kim, J, Helibron, K, Kia, DA, Hemani, G, Xue, A, Lawlor, DA , Davey Smith, G, Duran, R, Gan-Or, Z, Blauwendraat, C, Gibbs, JR, Hinds, DA, Yang, J, Visscher, PM, Cuzick, J, Morris, H, Hardy, J, Wood, N, Nalls, MA, Singleton, AB, International Parkinson's Disease Genomics Consortium (IPDGC) & the 23 and Me Research Team 2019, 'The Parkinson’s Disease Mendelian Randomization Research Portal', Movement Disorders, vol. 34, no. 12, pp. 1864 - 1872. https://doi.org/10.1002/mds.27873

TY - JOUR

T1 - The Parkinson’s Disease Mendelian Randomization Research Portal

AU - Noyce, Alastair J.

AU - Bandres-Ciga, Sara

AU - Kim, Jonggeol

AU - Helibron, Karl

AU - Kia, Demis A.

AU - Hemani, Gibran

AU - Xue, Angil

AU - Lawlor, Debbie A

AU - Davey Smith, George

AU - Duran, Raquel

AU - Gan-Or, Ziv

AU - Blauwendraat, Cornelis

AU - Gibbs, J Raphael

AU - Hinds, David A.

AU - Yang, Jian

AU - Visscher, Peter M

AU - Cuzick, Jack

AU - Morris, Huw

AU - Hardy, John

AU - Wood, Nicholas

AU - Nalls, Mike A

AU - Singleton, Andrew B

AU - International Parkinson's Disease Genomics Consortium (IPDGC)

AU - the 23 and Me Research Team

PY - 2019/12/17

Y1 - 2019/12/17

N2 - BackgroundMendelian randomization is a method for exploring observational associations to find evidence of causality. ObjectiveTo 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.MethodsWe 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. ResultsWe 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.DiscussionWe 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.

AB - BackgroundMendelian randomization is a method for exploring observational associations to find evidence of causality. ObjectiveTo 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.MethodsWe 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. ResultsWe 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.DiscussionWe 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.

KW - public resource

KW - risk factor

KW - Parkinson’s disease

KW - Mendelian randomization

U2 - 10.1002/mds.27873

DO - 10.1002/mds.27873

M3 - Article (Academic Journal)

C2 - 31659794

SN - 0885-3185

VL - 34

SP - 1864

EP - 1872

JO - Movement Disorders

JF - Movement Disorders

IS - 12

ER -

The Parkinson’s Disease Mendelian Randomization Research Portal

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Keywords

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Projects

8073 MRC IEU - Programme 6

IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

NIHR BRC Translational Population Health

Cite this