The combined effect of lifestyle factors and polygenic scores on age at onset in Parkinson's disease.
The combined effect of lifestyle factors and polygenic scores on age at onset in Parkinson's disease.
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生活方式因素和多基因评分对帕金森病发病年龄的综合影响。
DOI：
10.1101/2023.08.25.23294466
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Trinh,Joanne
中科院分区：
文献类型：
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作者：
Gabbert,Carolin;Blöbaum,Leonie;Lüth,Theresa;König,InkeR;Caliebe,Amke;Koch,Sebastian;Björn-Hergen,Laabs;Klein,Christine;Trinh,Joanne
本研究的目的是探讨帕金森病（PD）特异性多基因评分（PGS）和保护性生活方式因素与发病年龄（AAO）之间的关系。我们纳入了来自AMP-PD、PPMI和Fox Insight队列的4367例特发性PD患者、159例gba1 -PD患者和3090名欧洲血统的健康对照。采用线性和Cox比例风险模型评估PGS与生活方式因素对AAO的相关性。在特发性PD患者中，PGS与AAO呈负相关（β= - 1.07,p= 6 × 10-7）。与不使用相比，使用一种、两种或三种保护性生活方式因素可使危险比降低21% （p= 0.0001）、44% （p< 2 × 10-16）和55% （p< 2 × 10-16）。在线性回归中发现阿司匹林（β= 7.62,p= 9 × 10-7）和PGS （β= - 1.58,p= 0.0149）对AAO有加性效应，但无交互作用（p= 0.9993），烟草也有类似效应。相比之下，阿司匹林摄入量与AAO之间没有发现inGBA1-PD的关联（p < 0.05）。在我们的队列中，咖啡、烟草、阿司匹林和PGS是PD AAO的独立预测因子。此外，生活方式因素似乎比常见的遗传风险变异对AAO的影响更大，其中阿司匹林的影响最大。
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 withGBA1-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 inGBA1-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.