Genetic Variants Associated with Parkinson's Disease Found in 13% of Patients

核心概念

Genetic variants associated with Parkinson's disease are more common than previously thought, occurring in 13% of individuals with the disease.

摘要

The study examined genetic data from over 10,500 participants with Parkinson's disease (PD) enrolled in the PD GENEration study. The researchers found that reportable genetic variants were present in 12.9% of the 8,301 participants who had completed genetic testing.

The most common variants were found in the GBA1 gene (7.7%), followed by LRRK2 (2.4%) and PRKN (2.1%). Participants with GBA1 variants or presumed compound heterozygous or homozygous PRKN variants had an earlier age of PD onset compared to those with negative results.

The study also found that individuals with elevated genetic risk factors, such as early age of onset, high-risk ancestry, or a first-degree relative with PD, had an 18% positivity rate for genetic variants. The researchers noted that this was higher than expected, as they "did not anticipate the high positivity rate for genetic mutations, specifically the nearly 10% having a positive result even without any known genetic risk factors."

The findings highlight the importance of genetic testing and counseling for individuals with Parkinson's disease, as the presence of certain genetic variants can impact disease onset and progression.

统计

Reportable genetic variants were found in 1,070 (12.9%) of the 8,301 participants with Parkinson's disease.
GBA1 variants were the most frequently identified, found in 7.7% of participants.
LRRK2 variants were found in 2.4% of participants, and PRKN variants in 2.1%.
Participants with GBA1 variants or presumed compound heterozygous or homozygous PRKN variants had an earlier age at onset (58.6 and 38.6 years, respectively) compared to those with negative results (61.5 years).
Individuals with elevated genetic risk factors had an 18% positivity rate for genetic variants.

引用

"We did not anticipate the high positivity rate for genetic mutations, specifically the nearly 10% having a positive result even without any known genetic risk factors."
"Further, the speed at which participants enrolled in PD GENEration is a testament to the interest of people with PD to obtain data on their genetic status."

从中提取的关键见解

Genetic Variants in Parkinson's More Common Than Thought

by Edited Eve B... 在 www.medscape.com 08-20-2024

https://www.medscape.com/viewarticle/genetic-variants-parkinsons-more-common-than-thought-2024a1000f88

更深入的查询

How do the genetic variants identified in this study impact the clinical presentation and progression of Parkinson's disease?

The genetic variants identified in this study, particularly in genes like LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7, and VPS35, play a significant role in influencing the clinical presentation and progression of Parkinson's disease. For instance, individuals with GBA1 variants or certain PRKN variants were found to have an earlier age at onset (AAO) of the disease compared to those without these variants. This suggests that specific genetic mutations can lead to an earlier onset of Parkinson's disease. Additionally, carriers of SNCA variants also exhibited an earlier AAO, indicating the impact of genetic variations on disease manifestation. Understanding these genetic factors can help in predicting disease progression, tailoring treatment strategies, and providing personalized care for individuals with Parkinson's disease.

What are the potential limitations of the study's findings, given the relative lack of racial and ethnic diversity in the participant population?

One of the potential limitations of the study's findings is the relative lack of racial and ethnic diversity in the participant population. The study primarily focused on individuals from North America, which may not fully represent the genetic diversity of global populations. As a result, the findings may not be directly applicable to non-European populations, limiting the generalizability of the results. The lack of diversity could also lead to biases in the study, as certain genetic variants or risk factors prevalent in specific racial or ethnic groups may not have been adequately captured. To address this limitation, future studies should aim to include a more diverse participant population to ensure the comprehensive understanding of genetic factors influencing Parkinson's disease across different ethnicities.

What other genetic or environmental factors may contribute to the development of Parkinson's disease, and how could future research explore these factors?

In addition to the genetic variants identified in this study, other genetic and environmental factors may contribute to the development of Parkinson's disease. Genetic factors such as mutations in genes like SNCA, PINK1, and VPS35, which were also analyzed in the study, could play a role in disease susceptibility. Furthermore, environmental factors like exposure to pesticides, heavy metals, or traumatic brain injuries have been linked to an increased risk of Parkinson's disease. Future research could explore the interplay between genetic and environmental factors in disease development, as well as investigate epigenetic modifications that may influence Parkinson's disease risk. By conducting large-scale studies with diverse populations and utilizing advanced genomic technologies, researchers can gain a more comprehensive understanding of the complex etiology of Parkinson's disease.