TY - JOUR
T1 - The combined effect of lifestyle factors and polygenic scores on age at onset in Parkinson's disease
AU - Gabbert, Carolin
AU - Blöbaum, Leonie
AU - Lüth, Theresa
AU - König, Inke R
AU - Caliebe, Amke
AU - Sendel, Sebastian
AU - Laabs, Björn-Hergen
AU - Klein, Christine
AU - Trinh, Joanne
N1 - © 2024. The Author(s).
PY - 2024/6/25
Y1 - 2024/6/25
N2 - 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 (i.e., 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=8×10-7) and PGS (β=-1.63, p=0.0112) was found for AAO without an interaction (p=0.9789) in the linear regressions, and similar effects were seen for tobacco. Aspirin is shown to be a better predictor of AAO (R2=0.1740) compared to coffee and tobacco use (R2=0.0243, R2=0.0295) or the PGS (R2=0.0141). In contrast, no association between aspirin and AAO was found in GBA1-PD (p>0.05).INTERPRETATION: 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. External validation of our findings is needed.
AB - 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 (i.e., 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=8×10-7) and PGS (β=-1.63, p=0.0112) was found for AAO without an interaction (p=0.9789) in the linear regressions, and similar effects were seen for tobacco. Aspirin is shown to be a better predictor of AAO (R2=0.1740) compared to coffee and tobacco use (R2=0.0243, R2=0.0295) or the PGS (R2=0.0141). In contrast, no association between aspirin and AAO was found in GBA1-PD (p>0.05).INTERPRETATION: 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. External validation of our findings is needed.
U2 - 10.1101/2023.08.25.23294466
DO - 10.1101/2023.08.25.23294466
M3 - Journal articles
C2 - 37662355
SN - 2045-2322
VL - 14
SP - 14670
JO - Scientific Reports
JF - Scientific Reports
IS - 1
ER -
