Genetic and environmental factors in the cause of Parkinson's disease

BACKGROUND: Risk factors for Parkinson's disease (PD) can be more or less relevant to a population due to population-specific genetic architecture, local lifestyle habits, and environmental exposures. Therefore, it is essential to study PD at a local, regional, and continental scale in order to increase the knowledge on disease etiology. OBJECTIVE: We aimed to investigate the contribution of genetic and environmental factors to PD in a new Swedish case-control cohort. METHODS: PD patients (n=929) and matched population-based controls (n=935) from the southernmost county in Sweden were included in the cohort. Information on environmental exposures was obtained using questionnaires at inclusion. Genetic analyses included a genome-wide association study (GWAS), haplotype assessment, and a risk profile analysis using cumulative genetic risk scores. RESULTS: The cohort is a representative PD case-control cohort (64% men, mean age at diagnosis = 67 years, median Hoehn and Yahr score = 2.0), in which previously reported associations between PD and environmental factors, such as tobacco, could be confirmed. We describe the first GWAS of PD solely composed of PD patients from Sweden, and confirm associations to well-established risk alleles in SNCA. In addition, we identified a potential novel, population-specific PD risk variant in the PLPP4 locus (rs12771445) along with a risk haplotype in the region. CONCLUSIONS: This work provides an in-depth description of a new PD case-control cohort from southern Sweden in which we identified a potential novel PD risk locus, PLPP4. Replication studies are needed to determine whether the PLPP4 locus is associated with PD in Sweden, and on a global scale.

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Genetic and Environmental Factors Contributing to Parkinson's Disease: A Case-Control Study in the Cypriot Population

Frontiers in Neurology ◽

10.3389/fneur.2019.01047 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Andrea Georgiou ◽

Christiana A. Demetriou ◽

Yiolanda P. Christou ◽

Alexandros Heraclides ◽

Eleni Leonidou ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Environmental Factors ◽

Case Control Study ◽

Case Control ◽

Genetic And Environmental Factors ◽

Control Study

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Etiology of Parkinson's Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s031716710000319x ◽

2003 ◽

Vol 30 (S1) ◽

pp. S10-S18 ◽

Cited By ~ 27

Author(s):

Zhigao Huang ◽

Raúl de la Fuente-Fernández ◽

A. Jon Stoessl

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Environmental Factors ◽

Neurodegenerative Disorders ◽

Caffeine Intake ◽

Genetic Mutations ◽

Abnormal Protein ◽

Relative Contribution ◽

Genetic And Environmental Factors

There is growing recognition that Parkinson's disease (PD) is likely to arise from the combined effects of genetic predisposition as well as largely unidentified environmental factors. The relative contribution of each varies from one individual to another. Even in situations where more than one family member is affected, the predominant influence may be environmental. Although responsible for only a small minority of cases of PD, recently identified genetic mutations have provided tremendous insights into the basis for neurodegeneration and have led to growing recognition of the importance of abnormal protein handling in Parkinson's as well as other neurodegenerative disorders. Abnormal protein handling may increase susceptibility to oxidative stress; conversely, numerous other factors, including oxidative stress and impaired mitochondrial function can lead to impaired protein degradation. A limited number of environmental factors are known to be toxic to the substantia nigra; in contrast, some factors such as caffeine intake and cigarette smoking may protect against the development of PD, although the mechanisms are not established. We review the various genetic and environmental factors thought to be involved in PD, as well as the mechanisms that contribute to selective nigral cell death.

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Genetic and environmental factors interplay in Parkinson's disease

Progress in Neurology and Psychiatry ◽

10.1002/pnp.261 ◽

2013 ◽

Vol 17 (1) ◽

pp. 4-4

Author(s):

Alistair Church

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Environmental Factors ◽

Genetic And Environmental Factors

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Insights on Genetic and Environmental Factors in Parkinson’s Disease from a Regional Swedish Case-Control Cohort

Journal of Parkinson s Disease ◽

10.3233/jpd-212818 ◽

2021 ◽

pp. 1-20

Author(s):

Kajsa Brolin ◽

Sara Bandres-Ciga ◽

Cornelis Blauwendraat ◽

Håkan Widner ◽

Per Odin ◽

...

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Environmental Factors ◽

Genetic Risk ◽

Environmental Exposures ◽

Case Control ◽

Control Cohort ◽

Genome Wide ◽

Genetic And Environmental Factors

Background: Risk factors for Parkinson’s disease (PD) can be more or less relevant to a population due to population-specific genetic architecture, local lifestyle habits, and environmental exposures. Therefore, it is essential to study PD at a local, regional, and continental scale in order to increase the knowledge on disease etiology. Objective: We aimed to investigate the contribution of genetic and environmental factors to PD in a new Swedish case-control cohort. Methods: PD patients (n = 929) and matched population-based controls (n = 935) from the southernmost county in Sweden were included in the cohort. Information on environmental exposures was obtained using questionnaires at inclusion. Genetic analyses included a genome-wide association study (GWAS), haplotype assessment, and a risk profile analysis using cumulative genetic risk scores. Results: The cohort is a representative PD case-control cohort (64%men, mean age at diagnosis = 67 years, median Hoehn and Yahr score 2.0), in which previously reported associations between PD and environmental factors, such as tobacco, could be confirmed. We describe the first GWAS of PD solely composed of PD patients from Sweden, and confirm associations to well-established risk alleles in SNCA. In addition, we nominate an unconfirmed and potentially population-specific genome-wide significant association in the PLPP4 locus (rs12771445). Conclusion: This work provides an in-depth description of a new PD case-control cohort from southern Sweden, giving insights into environmental and genetic risk factors of PD in the Swedish population.

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Case-control study of interactions between genetic and environmental factors in Parkinson's disease

The Lancet ◽

10.1016/s0140-6736(05)61332-3 ◽

1998 ◽

Vol 352 (9145) ◽

pp. 1986-1987 ◽

Cited By ~ 43

Author(s):

Giuseppe De Palma ◽

Paola Mozzoni ◽

Antonio Mutti ◽

Stefano Calzetti ◽

Anna Negrotti

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Environmental Factors ◽

Case Control Study ◽

Case Control ◽

Genetic And Environmental Factors ◽

Control Study

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Chemically Induced Models of Parkinson’s Disease: History and Perspectives for the Involvement of Ferroptosis

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2020.581191 ◽

2020 ◽

Vol 14 ◽

Author(s):

Shuheng Wen ◽

Toshihiko Aki ◽

Kana Unuma ◽

Koichi Uemura

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Environmental Factors ◽

Chemical Inducers ◽

Chemical Models ◽

Chemically Induced ◽

History Of ◽

Genetic And Environmental Factors

Ferroptosis is a newly discovered form of necrotic cell death characterized by its dependency on iron and lipid peroxidation. Ferroptosis has attracted much attention recently in the area of neurodegeneration since the involvement of ferroptosis in Parkinson’s disease (PD), a major neurodegenerative disease, has been indicated using animal models. Although PD is associated with both genetic and environmental factors, sporadic forms of PD account for more than 90% of total PD. Following the importance of environmental factors, various neurotoxins are used as chemical inducers of PD both in vivo and in vitro. In contrast to other neurodegenerative diseases such as Alzheimer’s and Huntington’s diseases (AD and HD), many of the characteristics of PD can be reproduced in vivo by the use of specific neurotoxins. Given the indication of ferroptosis in PD pathology, several studies have been conducted to examine whether ferroptosis plays role in the loss of dopaminergic neurons in PD. However, there are still few reports showing an authentic form of ferroptosis in neuronal cells during exposure to the neurotoxins used as PD inducers. In this review article, we summarize the history of the uses of chemicals to create PD models in vivo and in vitro. Besides, we also survey recent reports examining the possible involvement of ferroptosis in chemical models of PD.

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