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Tendency towards being a “Morning person” increases risk of Parkinson’s disease: evidence from Mendelian randomisation

View ORCID ProfileAJ Noyce, DA Kia, K Heilbron, JEC Jepson, View ORCID ProfileG Hemani, The International Parkinson’s Disease Genomics Consortium, The 23andMe Research Team, DA Hinds, DA Lawlor, Smith G Davey, J Hardy, A Singleton, MA Nalls, NW Wood
doi: https://doi.org/10.1101/288241
AJ Noyce
1Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK
2Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
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  • ORCID record for AJ Noyce
DA Kia
2Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
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K Heilbron
323andMe, Inc., 899 W Evelyn Avenue, Mountain View, California 94041 USA
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JEC Jepson
4Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK
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G Hemani
5MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
6Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
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DA Hinds
323andMe, Inc., 899 W Evelyn Avenue, Mountain View, California 94041 USA
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DA Lawlor
5MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
6Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
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Smith G Davey
5MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
6Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
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J Hardy
2Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
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A Singleton
7Laboratory for Neurogenetics, National Institutes for Health, Bethesda, USA
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MA Nalls
7Laboratory for Neurogenetics, National Institutes for Health, Bethesda, USA
8Data Technica International, USA
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NW Wood
2Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
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  • For correspondence: n.wood@ucl.ac.uk
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Abstract

Background Circadian rhythm may play a role in neurodegenerative diseases such as Parkinson’s disease (PD). Chronotype is the behavioural manifestation of circadian rhythm and Mendelian randomisation (MR) involves the use of genetic variants to explore causal effects of exposures on outcomes. This study aimed to explore a causal relationship between chronotype and coffee consumption on risk of PD.

Methods Two-sample MR was undertaken using publicly available GWAS data. Associations between genetic instrumental variables (IV) and “morning person” (one extreme of chronotype) were obtained from the personal genetics company 23andMe, Inc., and UK Biobank, and consisted of the per-allele odds ratio of being a “morning person” for 15 independent variants. The per-allele difference in log-odds of PD for each variant was estimated from a recent meta-analysis. The inverse variance weight method was used to estimate an odds ratio (OR) for the effect of being a “morning person” on PD. Additional MR methods were used to check for bias in the IVW estimate, arising through violation of MR assumptions. The results were compared to analyses employing a genetic instrument of coffee consumption, because coffee consumption has been previously inversely linked to PD.

Findings Being a “morning person” was causally linked with risk of PD (OR 1⋅27; 95% confidence interval 1⋅06-1⋅51; p=0⋅012). Sensitivity analyses did not suggest that invalid instruments were biasing the effect estimate and there was no evidence for a reverse causal relationship between liability for PD and chronotype. There was no robust evidence for a causal effect of high coffee consumption using IV analysis, but the effect was imprecisely estimated (OR 1⋅12; 95% CI 0⋅89-1⋅42; p=0⋅22).

Interpretation We observed causal evidence to support the notion that being a “morning person”, a phenotype driven by the circadian clock, is associated with a higher risk of PD. Further work on the mechanisms is warranted and may lead to novel therapeutic targets.

Funding No specific funding source.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 26, 2018.
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Tendency towards being a “Morning person” increases risk of Parkinson’s disease: evidence from Mendelian randomisation
AJ Noyce, DA Kia, K Heilbron, JEC Jepson, G Hemani, The International Parkinson’s Disease Genomics Consortium, The 23andMe Research Team, DA Hinds, DA Lawlor, Smith G Davey, J Hardy, A Singleton, MA Nalls, NW Wood
bioRxiv 288241; doi: https://doi.org/10.1101/288241
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Tendency towards being a “Morning person” increases risk of Parkinson’s disease: evidence from Mendelian randomisation
AJ Noyce, DA Kia, K Heilbron, JEC Jepson, G Hemani, The International Parkinson’s Disease Genomics Consortium, The 23andMe Research Team, DA Hinds, DA Lawlor, Smith G Davey, J Hardy, A Singleton, MA Nalls, NW Wood
bioRxiv 288241; doi: https://doi.org/10.1101/288241

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