A Family History of Parkinson’s Disease and Its Effect on Other PD Risk Factors

1999 ◽  
Vol 18 (5) ◽  
pp. 270-278 ◽  
Author(s):  
Benjamin A. Rybicki ◽  
Christine C. Johnson ◽  
Edward L. Peterson ◽  
Gene X. Kortsha ◽  
Jay M. Gorell
2020 ◽  
Vol 91 (10) ◽  
pp. 1046-1054 ◽  
Author(s):  
Benjamin Meir Jacobs ◽  
Daniel Belete ◽  
Jonathan Bestwick ◽  
Cornelis Blauwendraat ◽  
Sara Bandres-Ciga ◽  
...  

ObjectiveTo systematically investigate the association of environmental risk factors and prodromal features with incident Parkinson’s disease (PD) diagnosis and the interaction of genetic risk with these factors. To evaluate whether existing risk prediction algorithms are improved by the inclusion of genetic risk scores.MethodsWe identified individuals with an incident diagnosis of PD (n=1276) and controls (n=500 406) in UK Biobank. We determined the association of risk factors with incident PD using adjusted logistic regression models. We constructed polygenic risk scores (PRSs) using external weights and selected the best PRS from a subset of the cohort (30%). The PRS was used in a separate testing set (70%) to examine gene–environment interactions and compare predictive models for PD.ResultsStrong evidence of association (false discovery rate <0.05) was found between PD and a positive family history of PD, a positive family history of dementia, non-smoking, low alcohol consumption, depression, daytime somnolence, epilepsy and earlier menarche. Individuals with the highest 10% of PRSs had increased risk of PD (OR 3.37, 95% CI 2.41 to 4.70) compared with the lowest risk decile. A higher PRS was associated with earlier age at PD diagnosis and inclusion of the PRS in the PREDICT-PD algorithm led to a modest improvement in model performance. We found evidence of an interaction between the PRS and diabetes.InterpretationHere, we used UK Biobank data to reproduce several well-known associations with PD, to demonstrate the validity of a PRS and to demonstrate a novel gene–environment interaction, whereby the effect of diabetes on PD risk appears to depend on background genetic risk for PD.


Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 430
Author(s):  
Steven R. Bentley ◽  
Ilaria Guella ◽  
Holly E. Sherman ◽  
Hannah M. Neuendorf ◽  
Alex M. Sykes ◽  
...  

Parkinson’s disease (PD) is typically sporadic; however, multi-incident families provide a powerful platform to discover novel genetic forms of disease. Their identification supports deciphering molecular processes leading to disease and may inform of new therapeutic targets. The LRRK2 p.G2019S mutation causes PD in 42.5–68% of carriers by the age of 80 years. We hypothesise similarly intermediately penetrant mutations may present in multi-incident families with a generally strong family history of disease. We have analysed six multiplex families for missense variants using whole exome sequencing to find 32 rare heterozygous mutations shared amongst affected members. Included in these mutations was the KCNJ15 p.R28C variant, identified in five affected members of the same family, two elderly unaffected members of the same family, and two unrelated PD cases. Additionally, the SIPA1L1 p.R236Q variant was identified in three related affected members and an unrelated familial case. While the evidence presented here is not sufficient to assign causality to these rare variants, it does provide novel candidates for hypothesis testing in other modestly sized families with a strong family history. Future analysis will include characterisation of functional consequences and assessment of carriers in other familial cases.


2021 ◽  
Vol 90 ◽  
pp. 161-164
Author(s):  
Seong-Min Choi ◽  
Soo Hyun Cho ◽  
Kyung Wook Kang ◽  
Jae-Myung Kim ◽  
Byeong C. Kim

2019 ◽  
Vol 19 (5-6) ◽  
pp. 211-217
Author(s):  
Muhammad Tufail

Background: Parkinson’s disease (PD) is one of the most common neurological disorders that mostly affect aged individuals. The common symptoms of PD are rest tremor, bradykinesia, and rigidity. Objectives: The present study was devised to find out the clinical features and risk factors associated with PD in a population of Khyber Pakhtunkhwa. Methods:A total of 600 PD patients and 1,200 control individuals took part in this study. The participants filled out a standard questionnaire. Results: This study found a significant association between PD and exposure to pesticides (p < 0.0001) and doing work on farms (p < 0.0001). The use of aldrin was significantly associated with PD (p < 0.0001). Furthermore, we also found that PD status was associated with individuals who have a history of depression, hypertension, head injury, and Alzheimer’s disease. This study also showed that the PD rate was lower in those who were using tobacco products. Conclusion: In this case-control study, we revealed some environmental and medical conditions that are linked with PD. To control the disease, we must minimize exposure to pesticides, and the government and scientific community should play their role.


2011 ◽  
Vol 15 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Stefano Zoccolella ◽  
Mariantonietta Savarese ◽  
Paolo Lamberti ◽  
Raffaele Manni ◽  
Claudio Pacchetti ◽  
...  

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