A paradoxical relationship between family history, onset age, and genetic risk in Parkinson's disease

Kristiansen, Madeleine; Maple‐Grødem, Jodi; Alves, Guido; Arepalli, Sampath; Hernandez, Dena G.; Iwaki, Hirotaka; Nalls, Mike A.; Singleton, Andrew B.; Tysnes, Ole‐Bjørn; Toft, Mathias; Pihlstrøm, Lasse

doi:10.1002/mds.27555

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…However, it is unclear whether smoking delays the AAO 25,31 . A similar phenomenon has been observed in patients with a family history of PD [32][33][34] . This study provides strong evidence to explain the real-world effects of smoking and family history of AAO.…”

Section: Discussionsupporting

confidence: 81%

Combined Associations of Genetic and Environmental Risk Factors in Age of Parkinson’s Disease Onset

Huang

Chen

et al. 2023

Preprint

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Substantial evidence has shown that the age at onset (AAO) of Parkinson’s disease (PD) is a major determinant of clinical heterogeneity. However, the mechanisms underlying heterogeneity in the AAO remain largely unknown. To investigate the independent association of genetic and environmental risk factors with the AAO of PD and their combined effects at a genome-wide level. A total of 3,156 patients with PD from the UK Biobank were included in this study. We evaluated the environmental risk factors associated with AAO using the Mann–Whitney U test and a generalized linear model. We further investigated the effects of genetic factors using linear regression analysis and their interactions with environmental risk factors using genome-wide by environment interaction studies. In addition to identifying previously reported environmental risk factors (smoking, non-steroidal anti-inflammatory drug intake, and family history of PD) associated with AAO, we found novel significant associations of physical activity (p < 0.0001) and excessive daytime sleepiness (p < 0.0001) with the AAO of PD. Individuals with a higher genetic risk had younger AAO (p = 3.91e-05). Additionally, we observed a nominally significant interaction between the polygenic risk scores and smoking for AAO (p = 0.0316). Specifically, several gene including ANGPT1 (p = 7.17e-07) and PLEKHA6 (p = 4.87e-06), suggestively significantly interacted with smoking to influence the AAO. Our data suggests that both genetic and environmental risk factors are associated with the AAO of PD and that there is a potential interaction between the two.

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Section: Discussionsupporting

confidence: 81%

Combined Associations of Genetic and Environmental Risk Factors in Age of Parkinson’s Disease Onset

Huang

Chen

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…But due to limited sample size, it is unclear whether smoking delays the AAO 21 , 28 . A similar controversy has been observed in patients with a family history of PD 29 – 31 . This study further provided some evidence to support that smoking is related to the later AAO of PD, while family history of PD is related to the earlier AAO of PD in European patients with PD.…”

Section: Discussionsupporting

confidence: 64%

Risk factors associated with age at onset of Parkinson’s disease in the UK Biobank

Huang,

Chen,

Wang

et al. 2024

npj Parkinsons Dis.

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Substantial evidence shown that the age at onset (AAO) of Parkinson’s disease (PD) is a major determinant of clinical heterogeneity. However, the mechanisms underlying heterogeneity in the AAO remain unclear. To investigate the risk factors with the AAO of PD, a total of 3156 patients with PD from the UK Biobank were included in this study. We evaluated the effects of polygenic risk scores (PRS), nongenetic risk factors, and their interaction on the AAO using Mann–Whitney U tests and regression analyses. We further identified the genes interacting with nongenetic risk factors for the AAO using genome-wide environment interaction studies. We newly found physical activity (P < 0.0001) was positively associated with AAO and excessive daytime sleepiness (P < 0.0001) was negatively associated with AAO, and reproduced the positive associations of smoking and non-steroidal anti-inflammatory drug intake and the negative association of family history with AAO. In the dose-dependent analyses, smoking duration (P = 1.95 × 10−6), coffee consumption (P = 0.0150), and tea consumption (P = 0.0008) were positively associated with AAO. Individuals with higher PRS had younger AAO (P = 3.91 × 10−5). In addition, we observed a significant interaction between the PRS and smoking for AAO (P = 0.0316). Specifically, several genes, including ANGPT1 (P = 7.17 × 10−7) and PLEKHA6 (P = 4.87 × 10−6), may influence the positive relationship between smoking and AAO. Our data suggests that genetic and nongenetic risk factors are associated with the AAO of PD and that there is an interaction between the two.

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A Theory of Bio-Quantum Genetics

Zhao

2024

JQIS

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The physical mechanism of heredity or inheritance of genes is a quantum mechanical and/or quantum computational process. A theory of bio-quantum genetics is established in this paper. Principle of Bio-quantum Genetics is suggested. I propose and define the soft-genes of genetics controlling the processes of heredity or inheritance of genes. This research deals with the quantum mechanisms of Mendel plant heredity and family inheritance as examples of bio-quantum genetics, deepening our understanding of heredity or inheritance. I believe that more contributions will be made to promote researches of bio-quantum genetics or quantum biology at large.

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A paradoxical relationship between family history, onset age, and genetic risk in Parkinson's disease

Cited by 3 publications

References 14 publications

Combined Associations of Genetic and Environmental Risk Factors in Age of Parkinson’s Disease Onset

Combined Associations of Genetic and Environmental Risk Factors in Age of Parkinson’s Disease Onset

Risk factors associated with age at onset of Parkinson’s disease in the UK Biobank

A Theory of Bio-Quantum Genetics

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