Faculty Opinions recommendation of TOMM40 and APOE common genetic variants are not Parkinson's disease risk factors.

2013 ◽  
Author(s):  
W Sue Griffin
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Disease Risk ◽  
Common Genetic Variants

TOMM40 and APOE common genetic variants are not Parkinson's disease risk factors

2013 ◽  
Vol 34 (8) ◽  
pp. 2078.e1-2078.e2 ◽  
Author(s):  
Beata Peplonska ◽  
Krzysztof Safranow ◽  
Katarzyna Gaweda-Walerych ◽  
Aleksandra Maruszak ◽  
Krzysztof Czyzewski ◽  
...  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Disease Risk ◽  
Common Genetic Variants

scholarly journals Putative second hit rare genetic variants in families with seemingly GBA-associated Parkinson’s disease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Muhammad Aslam ◽  
Nirosiya Kandasamy ◽  
Anwar Ullah ◽  
Nagarajan Paramasivam ◽  
Mehmet Ali Öztürk ◽  
...  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Rare Variants ◽  
Alpha Synuclein ◽  
Younger Age ◽  
Targeted Treatments ◽  
Genes Encoding ◽  
Rare Genetic Variants

AbstractRare variants in the beta-glucocerebrosidase gene (GBA1) are common genetic risk factors for alpha synucleinopathy, which often manifests clinically as GBA-associated Parkinson’s disease (GBA-PD). Clinically, GBA-PD closely mimics idiopathic PD, but it may present at a younger age and often aggregates in families. Most carriers of GBA variants are, however, asymptomatic. Moreover, symptomatic PD patients without GBA variant have been reported in families with seemingly GBA-PD. These observations obscure the link between GBA variants and PD pathogenesis and point towards a role for unidentified additional genetic and/or environmental risk factors or second hits in GBA-PD. In this study, we explored whether rare genetic variants may be additional risk factors for PD in two families segregating the PD-associated GBA1 variants c.115+1G>A (ClinVar ID: 93445) and p.L444P (ClinVar ID: 4288). Our analysis identified rare genetic variants of the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families. In comparison to the wild-type proteins, variant DNAJB6 and PSAP proteins show altered functions in the context of cellular alpha-synuclein homeostasis when expressed in reporter cells. Furthermore, the segregation pattern of the rare variants in the genes encoding DNAJB6 and PSAP indicated a possible association with PD in the respective families. The occurrence of second hits or additional PD cosegregating rare variants has important implications for genetic counseling in PD families with GBA1 variant carriers and for the selection of PD patients for GBA targeted treatments.

Parkinson's Disease Genetics and Pathophysiology

2021 ◽  
Vol 44 (1) ◽  
pp. 87-108
Author(s):  
Gabriel E. Vázquez-Vélez ◽  
Huda Y. Zoghbi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Neurodegenerative Disorder ◽  
Disease Risk ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Disease Modifying ◽  
Common Neurodegenerative Disorder

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by degeneration of the substantia nigra pars compacta and by accumulation of α-synuclein in Lewy bodies. PD is caused by a combination of environmental factors and genetic variants. These variants range from highly penetrant Mendelian alleles to alleles that only modestly increase disease risk. Here, we review what is known about the genetics of PD. We also describe how PD genetics have solidified the role of endosomal, lysosomal, and mitochondrial dysfunction in PD pathophysiology. Finally, we highlight how all three pathways are affected by α-synuclein and how this knowledge may be harnessed for the development of disease-modifying therapeutics.

scholarly journals Risk of Falls in Parkinson’s Disease: A Cross-Sectional Study of 160 Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Ana Contreras ◽  
Francisco Grandas
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Risk ◽  
Cross Sectional Study ◽  
Operating Characteristics ◽  
Balance Test ◽  
Cross Sectional ◽  
Risk Of Falls ◽  
Risk Factors For Falling

Falls are a major source of disability in Parkinson’s disease. Risk factors for falling in Parkinson’s disease remain unclear. To determine the relevant risk factors for falling in Parkinson’s disease, we screened 160 consecutive patients with Parkinson’s disease for falls and assessed 40 variables. A comparison between fallers and nonfallers was performed using statistical univariate analyses, followed by bivariate and multivariate logistic regression, receiver-operating characteristics analysis, and Kaplan-Meier curves. 38.8% of patients experienced falls since the onset of Parkinson’s disease (recurrent in 67%). Tinetti Balance score and Hoehn and Yahr staging were the best independent variables associated with falls. The Tinetti Balance test predicted falls with 71% sensitivity and 79% specificity and Hoehn and Yahr staging with 77% sensitivity and 71% specificity. The risk of falls increased exponentially with age, especially from 70 years onward. Patients aged >70 years at the onset of Parkinson’s disease experienced falls significantly earlier than younger patients.

Parkinson's disease risk factors: genetic, environmental, or both?

2005 ◽  
Vol 27 (2) ◽  
pp. 206-208 ◽  
Author(s):  
Mohamed Farouk Allam ◽  
Amparo Serrano Del Castillo ◽  
Rafael Fernández-Crehuet Navajas
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Risk

scholarly journals Association of common genetic variants of HOMER1 gene with levodopa adverse effects in Parkinson’s disease patients

2013 ◽  
Vol 14 (3) ◽  
pp. 289-294 ◽  
Author(s):  
A F Schumacher-Schuh ◽  
V Altmann ◽  
M Rieck ◽  
L Tovo-Rodrigues ◽  
T L Monte ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Effects ◽  
Genetic Variants ◽  
Common Genetic Variants

The epidemiology of Parkinson's disease: risk factors and prevention

2016 ◽  
Vol 15 (12) ◽  
pp. 1257-1272 ◽  
Author(s):  
Alberto Ascherio ◽  
Michael A Schwarzschild
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Risk

scholarly journals RIC3 variants are not associated with Parkinson's Disease in large European, Latin American, or East Asian cohorts

2021 ◽  
Author(s):  
Kajsa Brolin ◽  
Sara Bandres Ciga ◽  
Hampton Leonard ◽  
Mary B Makarious ◽  
Cornelis Blauwendraat ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Latin American ◽  
Rare Variants ◽  
Neurodegenerative Disorder ◽  
Disease Risk ◽  
East Asian ◽  
European Ancestry ◽  
Common Genetic Variants

Parkinson's disease (PD) is a complex neurodegenerative disorder in which both rare and common genetic variants contribute to disease risk. Multiple genes have been reported to be linked to monogenic PD, but these only explain a fraction of the observed familial aggregation. Rare variants in RIC3 have been suggested to be associated with PD in the Indian population. However, replication studies yielded inconsistent results. We further investigate the role of RIC3 variants in PD in European cohorts using individual-level genotyping data from 14,671 PD patients and 17,667 controls, as well as whole-genome sequencing data from 1,615 patients and 961 controls. We also investigated RIC3 using summary statistics from a Latin American cohort of 1,481 individuals, and from a cohort of 31,575 individuals of East Asian ancestry. We did not identify any association between RIC3 and PD in any of the cohorts. However, more studies of rare variants in non-European ancestry populations, in particular South Asian populations, are necessary to further evaluate the world-wide role of RIC3 in PD etiology.

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