The Parkinson’s phenome—traits associated with Parkinson’s disease in a broadly phenotyped cohort

Abstract

In order to systematically describe the Parkinson’s disease phenome, we performed a series of 832 cross-sectional case-control analyses in a large database. Responses to 832 online survey-based phenotypes including diseases, medications, and environmental exposures were analyzed in 23andMe research participants. For each phenotype, survey respondents were used to construct a cohort of Parkinson’s disease cases and age-matched and sex-matched controls, and an association test was performed using logistic regression. Cohorts included a median of 3899 Parkinson’s disease cases and 49,808 controls, all of European ancestry. Highly correlated phenotypes were removed and the novelty of each significant association was systematically assessed (assigned to one of four categories: known, likely, unclear, or novel). Parkinson’s disease diagnosis was associated with 122 phenotypes. We replicated 27 known associations and found 23 associations with a strong a priori link to a known association. We discovered 42 associations that have not previously been reported. Migraine, obsessive-compulsive disorder, and seasonal allergies were associated with Parkinson’s disease and tend to occur decades before the typical age of diagnosis for Parkinson’s disease. The phenotypes that currently comprise the Parkinson’s disease phenome have mostly been explored in relatively small purpose-built studies. Using a single large dataset, we have successfully reproduced many of these established associations and have extended the Parkinson’s disease phenome by discovering novel associations. Our work paves the way for studies of these associated phenotypes that explore shared molecular mechanisms with Parkinson’s disease, infer causal relationships, and improve our ability to identify individuals at high-risk of Parkinson’s disease.

Parkinson’s disease determinants, prediction and gene–environment interactions in the UK Biobank

“…In a recent paper from some members of this group, novel cross-sectional associations with PD were reported for migraine and epilepsy. 5 Here, we have not only replicated the association with epilepsy but also demonstrated a temporal relationship with incident PD. Whether the association is driven by epilepsy, chronic use of antiepileptic drugs or residual confounding remains to be determined.…”

Parkinson’s disease determinants, prediction and gene-environment interactions in the UK Biobank

“…In a recent paper from some members of this group, 'novel' cross-sectional associations with PD were reported for migraine and epilepsy 8 . Here we have not only replicated the association with epilepsy, but we have also demonstrated a temporal relationship with incident PD.…”

“…Separately, there exists good epidemiological evidence to support a role for potentiallymodifiable exposures including pesticide exposure, head injury, and potentially protective factors such as smoking, and drinking alcohol or caffeinated drinks 5,6,7,8 . Various comorbidities, such type 2 diabetes, and prodromal symptoms are more common among individuals who are subsequently diagnosed with PD, including anosmia, anxiety, depression, constipation, REM sleep behaviour disorder (RBD) and erectile dysfunction 7,8 . There are several examples of approaches that are being used in research settings to model the risk of PD prospectively [9][10][11] .…”

The Association Between Type 2 Diabetes Mellitus and Parkinson’s Disease

“…To make matters more confusing, a meta-analysis of fourteen case-control studies concluded that T2DM was associated with a reduced risk of PD (summary odds ratio 0.75) [36]. A very large, recent, cross-sectional study using self-reported information also found T2DM to be negatively associated with PD [37]. However, whilst cohort studies may be prone to biases as outlined above, cross-sectional and retrospective case-control studies may have additional design issues that bias effect estimates.…”