The Parkinson's Disease Mendelian Randomization Research Portal.
Adult
Aged
Aged, 80 and over
Causality
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Mendelian Randomization Analysis
/ methods
Middle Aged
Parkinson Disease
/ genetics
Phenotype
Polymorphism, Single Nucleotide
/ genetics
Risk Factors
Tea
Television
Treatment Outcome
Vital Capacity
Mendelian randomization
Parkinson's disease
public resource
risk factor
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
11
04
2019
revised:
05
08
2019
accepted:
04
09
2019
pubmed:
30
10
2019
medline:
23
6
2020
entrez:
30
10
2019
Statut:
ppublish
Résumé
Mendelian randomization is a method for exploring observational associations to find evidence of causality. 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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31659794
doi: 10.1002/mds.27873
pmc: PMC6973052
doi:
Substances chimiques
Tea
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1864-1872Subventions
Organisme : Medical Research Council
ID : MR/K01417X/1
Pays : United Kingdom
Organisme : Intramural Research Program of the National Institutes of Health
ID : Z01-ES101986
Pays : International
Organisme : Parkinson's UK
ID : G-0907
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : Intramural Research Program of the National Institutes of Health
ID : 1ZIA-NS003154
Pays : International
Organisme : Medical Research Council
ID : MR/N026004/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 208806/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701075
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0901254
Pays : United Kingdom
Organisme : Intramural Research Program of the National Institutes of Health
ID : Z01-AG000949-02
Pays : International
Organisme : Medical Research Council
ID : MR/L501542/1
Pays : United Kingdom
Informations de copyright
© 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Références
Neurology. 2017 Oct 24;89(17):1795-1803
pubmed: 28954882
PLoS One. 2015 Jun 29;10(6):e0131778
pubmed: 26121579
Geriatr Gerontol Int. 2014 Apr;14(2):430-9
pubmed: 23879665
Elife. 2018 May 30;7:
pubmed: 29846171
Stat Methods Med Res. 2017 Oct;26(5):2333-2355
pubmed: 26282889
Mov Disord. 2015 Oct;30(12):1600-11
pubmed: 26474317
Int J Epidemiol. 2015 Apr;44(2):512-25
pubmed: 26050253
Stat Med. 2008 Apr 15;27(8):1133-63
pubmed: 17886233
Int J Epidemiol. 2018 Aug 1;47(4):1264-1278
pubmed: 29961852
Nat Genet. 2017 Oct;49(10):1511-1516
pubmed: 28892059
Nat Genet. 2014 Sep;46(9):989-93
pubmed: 25064009
Genet Epidemiol. 2016 May;40(4):304-14
pubmed: 27061298
PLoS Med. 2017 Jun 13;14(6):e1002314
pubmed: 28609445
Lancet Neurol. 2019 Dec;18(12):1091-1102
pubmed: 31701892
Int J Epidemiol. 2013 Oct;42(5):1497-501
pubmed: 24159078
Br J Nutr. 2000 Feb;83(2):115-22
pubmed: 10743490
Int J Epidemiol. 2011 Jun;40(3):537-62
pubmed: 21807641
Mov Disord. 2017 Jul;32(7):983-990
pubmed: 28520211
PLoS Genet. 2010 Feb 26;6(2):e1000864
pubmed: 20195508
Hum Mol Genet. 2014 Sep 15;23(R1):R89-98
pubmed: 25064373
Cell Tissue Res. 2018 Jul;373(1):9-20
pubmed: 29536161
Ageing Res Rev. 2014 Mar;14:19-30
pubmed: 24503004
Ann Neurol. 2012 Dec;72(6):893-901
pubmed: 23071076
Mol Psychiatry. 2015 May;20(5):647-656
pubmed: 25288136
Hum Mol Genet. 2018 Aug 1;27(R2):R195-R208
pubmed: 29771313
Nature. 2015 Feb 12;518(7538):197-206
pubmed: 25673413