Heilbron, K;
Jensen, MP;
Bandres-Ciga, S;
Fontanillas, P;
Blauwendraat, C;
Nalls, MA;
Singleton, AB;
... 23andMe Research Team; + view all
(2021)
Unhealthy Behaviours and Risk of Parkinson's Disease: A Mendelian Randomisation Study.
Journal of Parkinson's Disease
10.3233/JPD-202487.
(In press).
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Abstract
Background: Tobacco smoking and alcohol intake have been identified in observational studies as potentially protective factors against developing Parkinson’s disease (PD); the impact of body mass index (BMI) on PD risk is debated. Whether such epidemiological associations are causal remains unclear. Mendelian randomsation (MR) uses genetic variants to explore the effects of exposures on outcomes; potentially reducing bias from residual confounding and reverse causation. Objective: Using MR, we examined relationships between PD risk and three unhealthy behaviours: tobacco smoking, alcohol intake, and higher BMI. Methods: 19,924 PD cases and 2,413,087 controls were included in the analysis. We performed genome-wide association studies to identify single nucleotide polymorphisms associated with tobacco smoking, alcohol intake, and BMI. MR analysis of the relationship between each exposure and PD was undertaken using a split-sample design. Results: Ever-smoking reduced the risk of PD (OR 0.955; 95%confidence interval [CI] 0.921–0.991; p = 0.013). Higher daily alcohol intake increased the risk of PD (OR 1.125, 95%CI 1.025–1.235; p = 0.013) and a 1 kg/m2 higher BMI reduced the risk of PD (OR 0.988, 95%CI 0.979–0.997; p = 0.008). Sensitivity analyses did not suggest bias from horizontal pleiotropy or invalid instruments. Conclusion: Using split-sample MR in over 2.4 million participants, we observed a protective effect of smoking on risk of PD. In contrast to observational data, alcohol consumption appeared to increase the risk of PD. Higher BMI had a protective effect on PD, but the effect was small.
| Type: | Article |
|---|---|
| Title: | Unhealthy Behaviours and Risk of Parkinson's Disease: A Mendelian Randomisation Study |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3233/JPD-202487 |
| Publisher version: | https://doi.org/10.3233/JPD-202487 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Parkinson’s disease, 23andMe, smoking, alcohol, BMI |
| 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 |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10132326 |
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