PDF(Pubmed)
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.
摘要：
这项研究的目的是调查帕金森病（PD）特异性多基因评分（PGS）与PD发病年龄（AAO）的保护性生活方式因素之间的关系。我们纳入了4367例特发性PD患者的数据，159例GBA1-PD患者，和来自AMP-PD的3090名欧洲血统健康对照，PPMI,和FoxInsight队列。用线性和Cox比例风险模型评估PGS与AAO生活方式因素之间的关联。特发性PD患者的PGS与AAO呈负相关（β=-1.07，p=6×10-7）。使用一个，两个,或三个保护性生活方式因素显示危险比降低了21％（p=0.0001），44%(p<2×10-16)，和55%(p<2×10-16)，相比没有用。在线性回归中发现了AAO的阿司匹林（β=7.62，p=9×10-7）和PGS（β=-1.58，p=0.0149）的累加效应，而没有相互作用（p=0.9993）。烟草也有类似的效果。相比之下,在GBA1-PD中未发现阿司匹林摄入量与AAO之间存在相关性(p>0.05)。在我们的队列中，咖啡,烟草,阿司匹林,和PGS是PDAAO的独立预测因子。此外,生活方式因素对AAO的影响似乎大于常见的遗传风险变异,阿司匹林的影响最大.
