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.

Fig. 1

Forest plot of odds ratios between Parkinson’s disease and associated phenotypes. Forest plot of the odds ratios (ORs) ± 95% confidence intervals (CIs) for 69 phenotypes from the following groups that were significantly associated with PD: personality, neurological, diet, autonomic, psychiatric, sleep, musculoskeletal, or cardiovascular/metabolic. Colors denote the extent to which an association between PD and the phenotype had previously been studied. If the upper 95% CI of an association was greater than four, data are presented as text. The dashed line represents an OR of one—no association with PD. To help clarify the directionality of associations, comprehensive phenotype definitions can be found in the Supplementary Data 2. GERD, gastro-esophageal reflux disease; IBS, irritable bowel syndrome; REM, rapid eye movement

Fig. 2

Forest plot of odds ratios between Parkinson’s disease and associated phenotypes. Forest plot of the odds ratios (ORs) ± 95% confidence intervals (CIs) for 53 phenotypes from the following groups that were significantly associated with PD: environment, drug usage, urinary/renal, morphology, immune, skin, sensation, reproductive, overall health, other, music, lifestyle, eyes, cancer, hair, or cosmetic surgery. Colors denote the extent to which an association between PD and the phenotype had previously been studied. If the upper 95% CI of an association was greater than four, data are presented as text. The dashed line represents an OR of one—no association with PD. To help clarify the directionality of associations, comprehensive phenotype definitions can be found in the Supplementary Data 2. DDT, dichlorodiphenyltrichloroethane; LASIK, laser-assisted in situ keratomileusis