New research suggests your daily coffee habit might help delay the onset of Parkinson’s disease—but don’t count on it to lower your risk or slow its progression.
Study: Coffee consumption is associated with later age-at-onset of Parkinson’s disease. Image Credit: Kittyfly / Shutterstock
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
In a recent research paper uploaded to the medRxiv preprint* server, researchers investigated the causal relationship between coffee consumption and age-at-onset (AAO) of Parkinson's disease (PD).
They used Mendelian randomization (MR) and genetic correlation analyses with publicly available genome-wide association study (GWAS) data from an extensive European cohort (n = 27,693) to determine whether coffee consumption causally affects PD age-at-onset (AAO).
To ensure holistic data coverage, they investigated the associations between coffee consumption, PD genetic factors, PD progression, and overall PD risk. Polygenic risk score (PRS) analysis was also performed to confirm that genetic predisposition does not drive the observed effect. Mendelian randomization models comprised the bulk of the analyses.
Study findings did not find an association between coffee consumption and increased PD risk or progression. Notably, Mendelian randomization results highlighted that increased coffee consumption was causally linked to delayed PD AAO. Sensitivity and heterogeneity tests confirmed the robustness of these findings, strengthening the validity of the causal inference. These results suggest that coffee consumption may have a protective effect against the disease.
Background
Parkinson's disease (PD) is a neurological disorder characterized by the progressive death of motor neurons, resulting in movement impairment, tremors, stiffness, and reduced balance.
The disease is rare, affecting approximately 11.77 million individuals (2021 estimates), but its prevalence is rising at an alarming rate. While a definitive cause for the disease remains unknown, several factors are thought to contribute to its age-at-onset (AAO) and progression rate, particularly genetic predisposition and environmental exposures.
Parkinson's is an age-associated condition, with adults above the age of 60 at the highest disease risk. Unfortunately, no cure for PD has hitherto been discovered, prompting research aimed at delaying PD AAO.
Previous observational studies have suggested that coffee consumption may help reduce PD risk, but clinical trials have failed to verify these results, confounding scientific opinion.
Nevertheless, caffeine's chemical makeup may help protect against PD or delay its onset via at least two mechanisms: dopaminergic modulation and adenosine receptor antagonism. Notably, PD patients have been reported to have lower circulating caffeine levels than healthy individuals of the same age. This knowledge necessitates further study into the causal associations between coffee intake and PD outcomes.
About the preprint
The present preprint leverages genetic correlation and Mendelian randomization models to investigate the causal associations between coffee consumption (including amount) and PD outcomes (AAO, progression, and overall risk).
Study data was obtained from publicly available genome-wide association study (GWAS) repositories (n = 27,693; PD cases = 15,056, healthy controls = 12,637).
GWAS data from the UK Biobank was independently analyzed to verify genetic single nucleotide polymorphisms (SNPs) with PD potential. Notably, the entire study dataset was derived from individuals of European descent, limiting its global generalizability and necessitating further research in more diverse populations.
Mendelian randomization models were optimized to identify SNPs significantly associated with coffee consumption via the inverse variance-weighted (IVW) method. To strengthen causal inference, the researchers excluded pleiotropic SNPs that might confound the relationship between coffee intake and PD AAO. Sensitivity analyses (weighted median and MR-Egger) confirmed the robustness of these findings. Data heterogeneity was assessed using Cochran's Q test.
To verify that coffee consumption was not harmful (increased PD risk), polygenic risk scores (PRSs) were computed and adjusted for age, sex, and other identified principal components.
Study findings
Initial GWAS SNP analyses revealed 28 potential SNPs denoting an association between coffee consumption and PD AAO, hitherto referred to as instrumental variables (IVs). Of these, 16 were found to be pleiotropic and were therefore excluded from downstream analysis.
Mendelian randomization estimation of the remaining 12 IVs revealed a strong causal correlation between coffee consumption and PD AAO, with increased coffee consumption corresponding to delayed PD AAO.
Notably, PRS analyses found no association between coffee consumption and PD risk or clinical progression across motor (UPDRS3), non-motor (hyposmia, sleep), and cognitive (MMSE and MoCA) aspects, confirming that coffee does not accelerate disease progression.
Even more encouragingly, PRS analyses found no correlation between genetic predisposition and coffee consumption, suggesting that even individuals with a genetic predisposition to PD can safely consume coffee without influencing their disease trajectory.
Conclusions
The present study investigated the potential protective effects of coffee against PD and found that increased coffee consumption was causally linked to delayed PD onset (AAO), verifying the beneficial effects of the beverage.
However, while the study found no evidence that coffee consumption increases PD risk or accelerates disease progression, it does not directly assess the safety of coffee consumption for clinical PD patients. The authors also acknowledge that residual pleiotropy cannot be entirely ruled out.
While the large study cohort is limited in its global generalizability (all participants are of European ancestry), the findings support coffee as an ideal target for future research to unravel the mechanisms underpinning its protective effects and explore potential clinical interventions.
Limitations and Future Directions
Although this study provides strong evidence of coffee’s role in delaying PD onset, several limitations must be considered. The research was restricted to individuals of European ancestry, limiting global applicability. Additionally, GWAS datasets for PD progression were relatively small and may have been underpowered to detect associations. Further investigations are needed in diverse populations, as well as studies examining potential sex-specific effects and interactions with PD therapies.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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