Gene4pd: A Comprehensive Genetic Database Of Parkinsons Disease
- 1National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China
- 2Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
- 3Mobile Health Ministry of EducationChina Mobile Joint Laboratory, Xiangya Hospital, Central South University, Changsha, China
- 4Center for Medical Genetics, Hunan Key Laboratory, School of Life Sciences, Central South University, Changsha, China
- 5Department of Pathogen Biology, School of Basic Medical Sciences, Central South University, Changsha, China
Toxic Substances That Have Been Linked To Parkinsons Disease
There are numerous environmental toxins that researchers have tied to the neurological disorders known as parkinson disease. Here are some that have been linked:
- Agent Orange This was a chemical defoliant used in Vietnam that is already tied to cancer. While there is no definitive link with Parkinsons, the VA at least believes that there is a possibility that the two are tied.
- Solvents Some studies have shown a link between Trichloroethylene, a substance contained in many solvents, and Parkinsons.
- PCBs polychlorinated biphenyls were extensively used in the 1970s. They have been often found in the brains of people who have suffered from Parkinsons.
- Pesticides and herbicides -substances such as insecticides, pesticides and herbicides contain chemicals that researchers have strongly linked with higher incidences of Parkinsons. One of the leading contributors is considered to be Paraquat. For information on Paraquat Parkinsons lawsuits, look here.
Genetic Risk For Parkinson’s Disease
If you have a genetic mutation associated with Parkinson’s, will you get the disease? Not necessarily. Some mutations carry a greater risk, but none bring a 100 percent chance of developing Parkinson’s disease. There are many Parkinson’s risk genes where a mutation means a very small increased likelihood of Parkinson’s. Researchers are looking for other factors that either push or protect someone with a gene mutation to or from having Parkinson’s. Your doctor and/or a genetic counselor can discuss the risk associated with different Parkinson’s genes and what your results may mean for you and your loved ones.
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Is Parkinsons Disease Hereditary The Facts
Hereditary diseases are passed from parent to child through genes, but is Parkinson’s one of them? Even though Parkinson’s can be passed genetically, this is rare. Here are some facts to shed some light on the issue:
- Only 15% of people with Parkinsons reported having someone in the family with the condition.
- Having a parent with Parkinsons disease only increases your risk of getting Parkinsons by 3%.
- Most people with early-onset Parkinson’s disease are likely to have inherited it.
So is Parkinsons disease hereditary? Yes, Parkinsons disease can be genetic. But thats not to say you will inherit the Parkinsons disease gene if your parent or grandparent has the condition. Nor does it mean you wont develop it just because it doesnt run in your family. Parkinson’s can be traced to various gene mutations, but most of the time the cause is unknown.
Data Annotation And Pag Prioritization
To investigate the functional genetic variants identified in patients with PD, ANNOVAR was used for comprehensive annotation based on definitions of transcripts from the RefSeq database. Based on the functional effects and minor allele frequency in the GnomAD database, the genetic variants were classified as follows: rare loss of function variants with MAF less than 0.01 rare deleterious missense variants with MAF less than 0.01 rare tolerate missense variants with MAF less than 0.01 and all remaining genetic variants. We used our previously developed program ReVe to predict deleterious missense variants with scores higher than 0.7, as previous studies.
To prioritize PAGs, we developed a scoring system combining the different types of genetic evidences as following. The rare variants assigned an evidence scores of 15 according to their functional effects and MAF. The CNVs were directly assigned an evidence score of 5 because they disrupted gene function. The PD-associated SNPs, DEGs, and DMGs were assigned an evidence scores of 13 based on their p-values. A combined evidence score for each gene was calculated by summing up the evidence scores of all integrated studies. All genes integrated in this study were classified into five grades: high confidence , strong associated , suggestive associated , minimal evidence , and uncertain evidence .
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Who Should Get Genetic Testing
Two groups might consider getting genetic testing, according to Gilbert:
- People with Parkinsons who want to know if they have a mutation they may pass along to their children
- Children and siblings of family members with Parkinsons who want to determine their genetic risk for the disease
Right now its not standard of care for everyone with Parkinsons to get genetic testing, she says. The likelihood that were going to find one of these mutations that is known already is small, and even if you have a mutation associated with Parkinsons, it doesnt mean that youre going to get the disease.
So, at this point, the value of getting tested depends on the individual. Doctors can provide this type of genetic evaluation, or people may turn to direct-to-consumer genetic testing, such as 23andMe. These tests, however, can be limited.
You have to be careful with those panels because theyre not very comprehensive, says Gilbert. They may test for only one or two gene variations.
Currently, 23andMe analyzes DNA from spit samples for a variant in LRRK2 and a variant in the GBA gene associated with the disorder. The company makes it clear that the exam does not diagnose the disease, and there are many other mutations to consider.
Parkinsons patient Paul Cannon, PhD, who works for 23andMe as its Parkinsons research community manager, took the test and found that he had neither of the genetic variations.
What Are The Benefits Of Genetic Testing
ESCAPE is developing a new therapy for patients with Parkinson’s disease caused by a mutation in theLRRK2 gene. It is hoped that this therapy may be able to stop or slow the progression of the disease. Since most people with Parkinsonâs disease have never been tested for LRRK2 mutations, ESCAPE is providing free genetic testing via mail which is an at-home saliva test. If a patient is found to have a mutation in theLRRK2 gene they will be invited to take part in certain clinical studies for patients with Parkinson’s disease and this specific gene mutation.
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How Does Environment Come Into It
Your environment is a hard one to pin down. Partly, that’s because it covers a lot of ground. It’s everything that’s not your genes, which could mean where you live, what you eat, chemicals you’ve come into contact with, and more.
Not only that, but it could take years for the effects from something in your environment to show up. So far, doctors have a lot of clues but no smoking gun. So you could have people who live or work in an area around chemicals tied to Parkinson’s, but many of them don’t get it.
Some research shows links between Parkinson’s and:
- Agent Orange, a chemical used to destroy trees and crops in the Vietnam War.
- Certain chemicals used in farming, such as insecticides, herbicides, and fungicides.
- Some metals and chemicals used in factories, such as manganese, lead, and trichlorethylene .
These can come into play based on where you live, what you do for work, or if you served in the military. Sometimes, these chemicals seep into well water, so that’s one more way they can affect you.
Identifying Risk Loci From Gwas
The underlying idea of a GWAS is based on the CDCV paradigm with the objective of detecting common variants in ethnically homogeneous populations. While critics suggest a genome-wide fishing expedition, the overwhelming majority of the genetics community would argue that the results gathered from such studies have marked a significant advancement from candidate gene studies and have driven the new era and concept of PD genetics. These advances are based on the premise that risk variants may occur within haplotype blocks shared with common variants through linkage disequilibrium. Since common variants can be tagged through genotyping marker arrays, risk variants in linkage disequilibrium should manifest an association by proxy with tagged common variants and ultimately with PD. By increasing sample size and genotype marker frequency, lower-risk variants with a lower population-attributable risk can be detected.
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What Causes Parkinsons Disease
Developing Parkinsons disease is not something that often happens on its own. Of course, there are genetic factors that could play a part in this neurological disorder. However, it is a combination of genetic and environmental factors that could lead to this disease.
In some cases, we have seen recent lawsuits that allege that exposure to certain chemicals has caused Parkinsons disease. Here, we will focus on how people could develop Parkinsons. That could give you an idea of whether you may have a possible lawsuit.
Genetic Testing: Whom To Test And How
The answer to the question of who should be tested is not trivial. To date, no formal testing guidelines have been developed by the Movement Disorder Society or any other PD alliance group. Out of all monogenic forms, mutations in LRRK2, Parkin, and PINK1 are the most likely to be encountered in clinical practice. In the following scenarios, genetic testing might prove useful to minimize further patient workup, to clarify treatment approaches, and/or to assist with future family planning: juvenile-onset PD irrespective of family history early-onset PD with atypical features and/or a positive family history of this disease or late-onset PD with a strong family history of PD . Guidelines published by the European Federation of the Neurological Sciences recommend screening LRRK2 for mutations in Europeans showing dominant inheritance of PD, testing for the LRRK2 p.G2019S mutation in familial and sporadic cases of PD in specific populations, and analysis of Parkin, PINK1, and DJ-1 in patients aged < 35 yr with recessively inherited PD .
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How You Lose Dopamine Production
Damaged nerve cells can be what results in a decreased ability of the brain to create dopamine. Generally, some kind of degradation of the brain cells will reduce dopamine production.
There is some genetic link to parkinsons disease. For example, specific genetic mutations can impact the dopamine production. Far more common is that exposure to something in the environment can impact the brain.
Genetic Classification Of Pd
In the current PD genetics nomenclature, 18 specific chromosomal regions, also called chromosomal locus, are termed PARK , and numbered in chronological order of their identification . In addition to being an incomplete list of known PD-related genes, this classification system, unfortunately, has a number of inconsistencies. It comprises confirmed loci, as well as those for which linkage or association could not be replicated . The causative gene has not yet been identified for all of the loci, nor do all of the identified genes contain causative or disease-determining mutations . Finally, one locus, PARK4, was designated as a novel chromosomal region associated with PD but was later found to be identical with PARK1 . It is noteworthy that some of the loci have been identified by genetic linkage analysis in large families, some based on the known function of the protein product of the gene they contain, yet others have been established by genome-wide association studies performed on a population level. A list of the PARK PD-related genes and loci is given in , along with their clinical classification, inheritance pattern , gene , status , and mode of identification.
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Parkinson’s Disease Diet And Nutrition
Maintaining Your Weight With Parkinson’s Disease
Malnutrition and weight maintenance is often an issue for people with Parkinson’s disease. Here are some tips to help you maintain a healthy weight.
- Weigh yourself once or twice a week, unless your doctor recommends weighing yourself often. If you are taking diuretics or steroids, such as prednisone, you should weigh yourself daily.
- If you have an unexplained weight gain or loss , contact your doctor. He or she may want to modify your food or fluid intake to help manage your condition.
- Avoid low-fat or low-calorie products. . Use whole milk, whole milk cheese, and yogurt.
Aao Is Associated With Multiple Genetic Components
The integrated genetic data and AAO data from the Gene4PD database provide an unprecedented opportunity to comprehensively identify the vital association between the AAO and PAGs on a large scale. Therefore, we analyzed 31 PAGs with more than five AAO items in each gene . After sorting by the median AAO of each gene, we found that 10 genes were associated with a juvenile-onset , 11 genes were associated with an early-onset , whereas another 10 genes were associated with a late-onset . Although different PAGs had specific AAO characteristics, we noted that there were large differences in the AAO for some genes, such as for PRKN, PINK1, SNCA, and LRRK2, suggesting that there are other factors that contribute to the AAO.
Figure 3. Association between Parkinsons disease-associated genes and age at onset. The association between age at onset and 31 Parkinsons disease-associated genes with more than five AAO items. The genes shown are sorted according to the median AAO or each gene. Association between AAO and 10 Parkinsons disease-associated genes with more three loss-of-function variants and deleterious missense variants.
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What Genes Are Linked To Parkinson’s Disease
In 1997, we studied a large family that came from a small town in Southern Italy in which PD was inherited from parent to child . We found the gene that caused their inherited Parkinson’s Disease and it coded for a protein called alpha-synuclein. If one studies the brains of people with PD after they die, one can see tiny little accumulations of protein called Lewy Bodies . Research has shown that there is a large amount of alpha-synuclein protein in the Lewy Bodies of people who have non-inherited PD as well as in the brains of people who have inherited PD. This immediately told us that alpha-synuclein played an important role in all forms of PD and we are still doing a lot of research to better understand this role.
Currently, seven genes that cause some form of Parkinson’s disease have been identified. Mutations in three known genes called SNCA , UCHL1 , and LRRK2 and another mapped gene have been reported in families with dominant inheritance. Mutations in three known genes, PARK2, PARK7 , and PINK1 have been found in affected individuals who had siblings with the condition but whose parents did not have Parkinson’s disease . There is some research to suggest that these genes are also involved in early-onset Parkinson’s disease or in dominantly inherited Parkinson’s disease but it is too early yet to be certain.
Pags Were Functionally Correlated
We performed a permutation test to assess the functional correlations of the 124 associated genes . Most of them were disease-causing genes or risk-genes from GWAS. As a result, we observed 48 of 63 high-confidence or strong PAGs that interacted with each other and had 203 interconnections , which was significantly higher than the random expectation. Similarly, the suggestive associated genes also significantly interacted with each other , suggesting they were functionally correlated. Furthermore, we observed 21 suggestive associated genes which interacted with high-confidence or strong PAGs with 74 connections , suggesting that the two classes of associated genes were also functionally correlated. These results demonstrate that the 124 genes were functionally associated with PD, although these results require further experimental validation.
Figure 2. Functional network and biological progresses of Parkinsons disease-associated genes. Functional network of closely related Parkinsons disease-associated genes based on the STRING database. Nodes are colored to show the associations, and the thickness of lines connecting nodes indicates the strength of the association between nodes. Biological progresses of gene ontology terms are involved in functional PPI network this network. The heavier the bar color is, the P-value more significant is.
What Is The Prognosis And Life Expectancy For Parkinson’s Disease
The severity of Parkinson’s disease symptoms and signs vary greatly from person to peson, and it is not possible to predict how quickly the disease will progress. Parkinson’s disease itself is not a fatal disease, and the average life expectancy is similar to that of people without the disease. Secondary complications, such as pneumonia, falling-related injuries, and choking can lead to death. Many treatment options can reduce some of the symptoms and prolong the quality of life.
Some Patients May Not Be Eligible To Take Part In The Free Genetic Testing Program
To speed up recruitment for a natural history program we are first focusing on patients who have a higher likelihood of testing positive for the mutated gene from the free genetic testing program. If a patient does not meet the criteria now, we will offer to contact them again should we open up the screening program to a wider population of Parkinsonâs patients.
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The Future Of Pd Genetics
We have identified three key concepts that need to be addressed to speed progress in future PD genetic research ventures. These include identifying and refining heritable risk, predicting the course of disease, and focusing on general data-centric approaches, all of which will facilitate building a bridge to a future intervention.
Identifying and refining heritable risk
Thus, for progress in this domain, we need continued investment in genome-wide association studies, a concerted effort to execute genetics in non-Caucasian populations, and a committed investment in large-scale whole-genome sequencing approaches. It will also be important to address how specific gene-environment interactions influence PD susceptibility. Recent genome-wide gene-environment interaction studies for complex traits are generally thought to be underpowered for detecting most gene-environment interaction effects. Therefore, assessing the role of gene-environment interactions in disease risk will involve data collection efforts across multi-centric, carefully recruited, and well-characterized datasets .
Predicting the course of disease
General data-centric approaches
For success in this domain, we require huge public facing projects that provide foundational data for the understanding of the molecular pathogenesis of PD an EnCode-style/scale project for PD would provide such a resource.