The combined effect of lifestyle factors and polygenic scores on age at onset in Parkinson’s disease
Carolin Gabbert, Leonie Blöbaum, Theresa Lüth, Inke R. König, Amke Caliebe, Sebastian Sendel, Björn‐Hergen Laabs, Christine Klein, Joanne Trinh
Abstract
Abstract The objective of this study was to investigate the association between a Parkinson’s disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age at onset (AAO) in PD. We included data from 4367 patients with idiopathic PD, 159 patients with GBA1 -PD, and 3090 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The association between PGS and lifestyle factors on AAO was assessed with linear and Cox proportional hazards models. The PGS showed a negative association with AAO ( β = − 1.07, p = 6 × 10 –7 ) in patients with idiopathic PD. The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21% ( p = 0.0001), 44% ( p < 2 × 10 –16 ), and 55% ( p < 2 × 10 –16 ), compared to no use. An additive effect of aspirin ( β = 7.62, p = 9 × 10 –7 ) and PGS ( β = − 1.58, p = 0.0149) was found for AAO without an interaction ( p = 0.9993) in the linear regressions, and similar effects were seen for tobacco. In contrast, no association between aspirin intake and AAO was found in GBA1 -PD ( p > 0.05). In our cohort, coffee, tobacco, aspirin, and PGS are independent predictors of PD AAO. Additionally, lifestyle factors seem to have a greater influence on AAO than common genetic risk variants with aspirin presenting the largest effect.