Combined Associations of Genetic and Environmental Risk Factors in Age of Parkinson’s Disease Onset

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

Abstract Substantial evidence has shown that the age at onset (AAO) of Parkinson’s disease (PD) is a major determinant of clinical heterogeneity. However, the mechanisms underlying heterogeneity in the AAO remain largely unknown. To investigate the independent association of genetic and environmental risk factors with the AAO of PD and their combined effects at a genome-wide level. A total of 3,156 patients with PD from the UK Biobank were included in this study. We evaluated the environmental risk factors associated with AAO using the Mann–Whitney U test and a generalized linear model. We further investigated the effects of genetic factors using linear regression analysis and their interactions with environmental risk factors using genome-wide by environment interaction studies. In addition to identifying previously reported environmental risk factors (smoking, non-steroidal anti-inflammatory drug intake, and family history of PD) associated with AAO, we found novel significant associations of physical activity (p ANGPT1 (p = 7.17e-07) and PLEKHA6 (p = 4.87e-06), suggestively significantly interacted with smoking to influence the AAO. Our data suggests that both genetic and environmental risk factors are associated with the AAO of PD and that there is a potential interaction between the two.

Related topics