Is there a linkage between genetic factors and the risk of individuals developing Parkinson’s disease?

INTRODUCTION
Introduction to the Problem
Parkinson’s disease is a degenerative disease that causes motor and non-motor symptoms over time. Tremors, delayed movement, the rigidity of the arms and legs, and shaking arms are some of the most prevalent symptoms of the condition, which is regarded as the second most common neurological disease after Alzheimer’s. Parkinson’s disease symptoms usually start gradually and get worse over time. As the disease progresses, a person may experience mobility and communication issues (Postuma et al., 2015). In addition, mental and behavioral changes and sleep troubles, melancholy, memory loss, and lethargy may occur. Through its progressive degenerative effects on movement and muscular function, the disease has a significant clinical impact on patients, their family members, and caregivers. According to studies, three out of every thousand adults over the age of 50 suffer from the illness (Westenberger, 2012).
Background of the Problem
In 1817, Dr. James Parkinson first described PD as “shaking palsy” (Polymeropoulos, 1996). According to studies, pathophysiological changes linked to the disease may start before motor symptoms appear. They can involve a wide range of nonmotor symptoms, such as sleep problems, depression, and cognitive issues (Westenberger, 2012).
Diseases have appeared and disappeared throughout history, while some have risen or reduced in occurrence. Such epidemiological patterns have been more pronounced in infectious diseases (for example, the elimination of smallpox). Still, they have also been seen in chronic disorders (such as reducing vitamin deficiencies and cardiovascular disease). Changing patterns in the epidemiology of neurological illnesses have been observed during the last three or four decades. In several high-income countries, the incidence of stroke and dementia has reduced (specifically in North America and Western Europe). Nonetheless, the risk of Parkinson’s disease has risen (Rocca, 2017; Rocca, 2018).
In the United States, The Parkinson’s Disease Foundations reports that approximately 1 million Americans currently live with the illness (Westenberger, 2012). Parkinson’s disease is estimated to affect 20 people out of every 100,000 people each year, with a typical presentation age of 60 years. In persons 60 years and older, the prevalence of Parkinson’s disease is estimated to be around 1%, increasing from 1% to 3% in those aged 80 and above. It is, however, crucial to note that these figures do not represent undiagnosed cases.
The unpredictable but noticeable course of Parkinson’s disease substantially impacts individuals, families, and society. The advanced and end-stage illness can result in significant consequences, such as pneumonia, often fatal (Postuma et al., 2015). Even though current treatment focuses on symptom management, research suggests that patients benefit from a multidisciplinary approach to care. An interdisciplinary approach is movement experts, social workers, pharmacists, and other healthcare professionals.
PD is linked to several risk factors and genetic abnormalities. Oxidative stress, the generation of free radicals, and various environmental pollutants are risk factors for the disease. Although only limited data exist to support the genetic associations of Parkinson’s disease with gene mutations, the variable prevalence suggests that these factors may play a role in the pathogenesis of the illness (Redensek, 2017).
Statement of the Problem
The problem is that it has become clear that Parkinson’s disease is a complex genetically heterogeneous disorder (Polymeropoulos, 1996). To illustrate how complicated it is, we may talk about 28 distinctive chromosomal areas associated with PD. Just six of these regions contain genetic makeup with mutations that lead to monogenic PD, a type of disease in which a single gene mutation is enough to cause symptoms. Even when considered together, the mutation in these six genes is responsible for only 3–5% of all sporadic disease instances (Westenberger, 2012). Instead, the genesis of Parkinson’s disease is multifaceted and results from a complex interaction of commonly unidentified components, including multiple genes, susceptibility variants’ altering effects, environmental factors, and gene-environment interactions. Alterations (or mutations) in specific genes are passed down or transmitted from one generation to another in some families. Researchers are still puzzled why some ethnic groups, such as Ashkenazi and Northern Africa Arab Berbers, are more likely to possess genes associated with Parkinson’s disease (Day, 2021).
Purpose of the Study
It’s critical to understand the role of genetics as a risk factor for Parkinson’s disease. Understanding how Parkinson’s disease is linked to genetics will help us better understand how the disease develops and, ultimately, how this could be managed or cured. Such knowledge may assist doctors (1) in recognizing the genes that are linked to Parkinson’s disease, (2) in identifying the people who are most likely to develop Parkinson’s disease, (3) in providing a platform for the discovery of novel possible targets for neuroprotective therapy. Through genetic mapping, (4) to determine how accurate gene mapping is for Parkinson’s disease, (5) to establish whether genetic mapping can help figure out what caused the gene mutation and how the condition progressed, (6) to stratify PD patients based on their genetic fingerprint and tailor their therapy and supporting measures accordingly.
Research Question
This project aims to answer the following question: Is there a linkage between genetic factors and the risk of individuals developing Parkinson’s disease?
Significance of the Study
One way to divide Parkinson’s disease is through genetics. Aetiologies, therapies, and prognoses for different subgroups may differ. Age of onset (early- vs. late-onset PD, with a cut-off of 50 years of age), family history (familial vs. sporadic PD), and pathogenic variations (monogenic vs. idiopathic PD) are all common stratification criteria for Parkinson’s disease (Dumitriu, 2012; Redensek, 2017). Because the linkage between genetic factors and the risk of individuals developing PD has not been realized fully, this research will add to the body of knowledge of this understanding. This is because understanding the genetic factor of the disease will impact its mapping and clinical care.
To begin, the research will aid in identifying the causal genes and highlighting critical biological processes in pathogenesis. As revealed by the study conducted by Nalls et al. (2015), this will aid early diagnosis and indicate the disease’s prognosis. Initial non-motor indicators mixed with genetic susceptibility may be an excellent way to identify people in the early phases of the illness. Only genetic testing for sporadic PD diagnosis or prediction of sporadic PD development is not specific or sensitive enough at this time. No known genetic component or combination of genetic variables can predict the onset of sporadic PD with certainty.
Second, it can accurately classify the disease presentations into groups with common genetic origins. This is critical for ‘precision medicine,’ which focuses on a patient’s precise disease subtype. It would also be fascinating to examine the relationship between illness progression and genetic abnormalities in genes involved in various pathways. To illustrate, GBA mutations or MAPT H1 allele status could be independent risk factors for cognitive impairment in PD patients, and knowing these statuses in patients could affect therapy options (Lill, 2016). Patients have only been divided into groups based on their phenotypes thus far (Fereshtehnejad, 2015).
Different combinations of genetic abnormalities, on the other hand, should be investigated in order to develop a method for stratifying PD patients depending on the cumulative effects of genetic predisposition factors within and across pathways. Patients with different genetic abnormalities may require different treatment approaches; thus, stratifying Parkinson’s disease patients based on their underpinning genetic conditions could be beneficial in a therapeutic context. Because we can stratify patients into groups based on their impaired pathways and treat them based on their underlying pathologic processes, this type of tailored treatment could become the treatment of choice in the future for PD. Physicians could tweak therapy for each group to get the best potential result (Fereshtehnejad, 2015).
Finally, as we better understand the impact of genetic variations on disease risk, onset, and progression, the implications and prognosis may be addressed openly with individuals, empowering them to make informed decisions.
Assumptions
The following assumptions are made regarding this project. (1) The review of the literature was conducted by one author, therefore, risking bias during the research assessment; (2) The research question will elicit reliable responses as the study will involve quantitative methodology involving large populations; (3) There is a similarity in the participant characteristics within the study as the research involves participants who have Parkinson’s disease; (4) The study can be replicated since it uses a systematic approach to data collection, analysis, and synthesizing.
Limitations
The majority of the studies used in the literature review were conducted in the United States, and their findings do not reflect the conclusions of other populations around the world. The majority of studies focus on older people. Still, it is crucial to study midlife because it is a critical age for developing PD, with substantial individual heterogeneity and long-standing consequences in later life stages. The neurological system’s health specifically is impacted by lifestyle choices made around middle age. Excessive stress in middle age, for example, is linked to self-care incapacity later in life. In terms of PD-specific behavioral impacts, in midlife, a physically and cognitively active lifestyle is linked to a lower risk of illness. It can lower the risk of Parkinson’s disease by up to 40%. As a result, detecting Parkinson’s disease in middle age through mapping would offer patients the opportunity to take advantage of the neuroprotective capabilities of positive behavioral and environmental factors, particularly physical activity (Redensek, 2017).
Another critical limitation is the degree of epigenetic variations in patients that exceeds variance between populations and cell makeup of the examined tissue. To evaluate the most suitable individuals, standardization must be enhanced. Furthermore, reliable web resources that are not peer-reviewed were excluded since they caused coding and data analysis problems.
Summary
Parkinson’s disease (PD) is a neurodegenerative brain illness with a significant genetic component. Parkinson’s disease (PD) is the second most prevalent degenerative brain illness after Alzheimer’s disease. Parkinson’s disease is thought to be caused by a combination of hereditary and environmental factors. The disease’s current clinical diagnosis is based on late-stage motor symptoms when many nigrostriatal dopaminergic neurons have already been destroyed. The study will analyze the type of genes linked to Parkinson’s disease and whether gene mapping can be used in the early diagnosis and treatment of the disease.
The second chapter contains a review of previous research, including its history and current situation, which will support the stated public health issue. This chapter will thus give a detailed explanation of prior research conducted on genetic factors like a predisposition for PD. Chapter three comprises the systematic literature review methodology consisting of the description of the participants and their inclusion and exclusion criteria.

References
Day, J. O., & Mullin, S. (2021). The genetics of Parkinson’s disease and implications for clinical practice. Genes, 12(7), 1006.
Dumitriu, A. (2012). Genome-wide expression and genomic data integration analyses in sporadic Parkinson’s disease. Boston University.
Klein, C., & Westenberger, A. (2012). Genetics of Parkinson’s disease. Cold Spring Harbor Perspectives in Medicine, 2(1).
Lill, C. M. (2016). Genetics of Parkinson’s disease. Molecular and Cellular Probes, 30(6), 386-396.
Nalls, M. A., Pankratz, N., Lill, C. M., Do, C. B., Hernandez, D. G., Saad, M., … & Singleton, A. B. (2014). Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nature Genetics, 46(9), 989-993.
Redenšek, S., Trošt, M., & Dolžan, V. (2017). Genetic determinants of Parkinson’s disease: Can they help to stratify the patients based on the underlying molecular defect? Frontiers in Aging Neuroscience, 9, 20.
Rocca, W. A. (2017). Time, sex, gender, history, and dementia. Alzheimer Disease and Associated Disorders, 31(1), 76.
Rocca, W. A. (2018). The future burden of Parkinson’s disease. Movement Disorders: Official Journal of the Movement Disorder Society, 33(1), 8.
Postuma, R. B., Berg, D., Stern, M., Poewe, W., Olanow, C. W., Oertel, W., … & Deuschl, G. (2015). MDS clinical diagnostic criteria for Parkinson’s disease. Movement Disorders, 30(12), 1591-1601.
Polymeropoulos, M. H., Higgins, J. J., Golbe, L. I., Johnson, W. G., Ide, S. E., Di Iorio, G., … & Duvoisin, R. C. (1996). Mapping of a gene for Parkinson`s disease to chromosome 4q21-q23. Science, 274(5290), 1197-1199.