Chromosome 12 and Environmental Factors in Parkinson's Disease: An All of Us Data Analysis

Parkinson's disease (PD) is a neurodegenerative disease that develops with age and is related to a decline in motor function. Studies suggest that the causes may be based on genetic dysfunction including PARK gene mutations and environmental factors.

To explore those factors, we used multivariable logistic regression to obtain odds ratios (ORs) and adjusted ORs by using the All of Us Dataset which contains genomic, blood test, and other environmental data.

On Chromosome 12, there were 3709 candidate genetic polymorphisms (GPs) that are associated with PD. Of those GPs, fourteen GPs had high ORs which are similar to the OR of the PARK8 gene G2019S mutation. Of those 3709 GPs, a 2.00-fold change in OR was observed in five GPs located at bases 53,711,362 (OR = 4.86, 95% CI [1.46, 16.18]), 31,281,818 (OR = 4.37, 95% CI [1.02, 18.82]), 101,921,705 (OR = 5.38, 95% CI [1.23, 23.51]), 47,968,795 (OR = 7.82, 95% CI [1.81, 33.83]), and 112,791,809 (OR = 8.05, 95% CI [1.85, 35.05]) by calcium, Vitamin D, and alcohol intake and were statistically significant.

The results suggest that the progression of some PD caused by certain GPs can be delayed or prevented by the environmental factors above. In February 2025, All of Us released the CT Dataset v.8 which has a 50% increase in the number of participants. Potentially, it may be possible to research more GPs and environmental factors. In future studies, we would like to explore other environmental factors and GPs on other chromosomes. It is believed that specific GPs may tailor current treatments and qualify patients for clinical trials. Additionally, genetic knowledge may help increase accuracy in clinical trials.