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Objective

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.

Methods

We included data from 4375 patients with idiopathic PD, 167 patients with GBA1-PD, and 3091 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The PGS was calculated based on a previously proposed composition of 1805 variants. The association between PGS and lifestyle factors (ie, coffee, tobacco, and aspirin) on AAO was assessed with linear and Cox proportional hazards models.

Results

The PGS showed a negative association with AAO (β=− 1.07, p= 6× 10− 7). The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21%(p= 0.0001), 45%(p< 2× 10− 16), and 55%(p< 2× 10− 16), respectively, compared to no use. An additive effect of aspirin (β= 7.61, p …