Study investigates genetic variants' role in increasing Parkinson's disease risk

October 6, 2012

Boston University School of Medicine (BUSM) investigators have led the first genome-wide evaluation of genetic variants associated with Parkinson's disease (PD). The study, which is published online in PLOS ONE, points to the involvement of specific genes and alterations in their expression as influencing the risk for developing PD.

Jeanne Latourelle, DSc, assistant professor of neurology at BUSM, served as the study's lead author and Richard H. Myers, PhD, professor of neurology at BUSM, served as the study's principal investigator and senior author.

A recent paper by the PD Genome Wide Association Study Consortium (PDGC) confirmed that an increased risk for PD was seen in individuals with genetic variants in or near the genes SNCA, MAPT, GAK/DGKQ, HLA and RIT2, but the mechanism behind the increased risk was not determined.

"One possible effect of the variants would be to change the manner in which a gene is expressed in the brains, leading to increased risk of PD," said Latourelle.

To investigate the theory, the researchers examined the relationship between PD-associated genetic variants and levels of gene expression in brain samples from the of 26 samples with known PD and 24 neurologically healthy control samples. was determined using a microarray that screened effects of genetic variants on the expression of genes located very close to the variant, called cis-effects, and genes that are far from the variant, such as those on a completely different chromosome, called trans-effects.

An analysis of the cis-effects showed that several genetic variants in the MAPT region showed a significant association to the expression of multiple nearby genes, including gene LOC644246, the duplicated genes LRRC37A and LRRC37A2 and the gene DCAKD. Significant cis-effects were also observed between variants in the HLA region on and two nearby genes HLA-DQA1 and HLA-DQA1. An examination of trans-effects revealed 23 DNA sequence variations that reached statistical significance involving variants from the SNCA, MAPT and RIT2 genes.

"The identification of the specific altered genes in PD opens opportunities to further study them in model organisms or cell lines with the goal of identifying drugs which may rectify the defects as treatment for PD," said Myers.

Explore further: Study finds genetic variation that protects against Parkinson's disease

More information: dx.plos.org/10.1371/journal.%20pone.0046199

Related Stories

Study finds genetic variation that protects against Parkinson's disease

August 31, 2011
An international team of researchers led by neuroscientists at Mayo Clinic in Florida has found a genetic variation they say protects against Parkinson's disease. The gene variants cut the risk of developing the disease by ...

Study examines association between Parkinson disease, cancer

September 3, 2012
A study that used a Utah genealogic database and a statewide cancer registry to examine the relationship between Parkinson disease (PD) and cancer suggests an increased risk of prostate cancer and melanoma in patients with ...

Genetic factors can predict the progression of Parkinson's disease

December 16, 2011
Parkinson's disease is marked by the abnormal accumulation of α-synuclein and the early loss of dopamine neurons in the substantia nigra region of the brain. A polymorphism in the promotor of α-synuclein gene known ...

Recommended for you

Investigating the most common genetic contributor to Parkinson's disease

October 19, 2017
LRRK2 gene mutations are the most common genetic cause of Parkinson's disease (PD), but the normal physiological role of this gene in the brain remains unclear. In a paper published in Neuron, Brigham and Women's Hospital ...

Scientists solve 3-D structure of key defense protein against Parkinson's disease

October 5, 2017
Scientists at the University of Dundee have identified the structure of a key enzyme that protects the brain against Parkinson's disease.

Novel protein interactions explain memory deficits in Parkinson's disease

September 26, 2017
A study published in the journal Nature Neuroscience describes the identification of a novel molecular pathway that can constitute a therapeutic target for cognitive defects in Parkinson's disease. The study showed that abnormal ...

Psychosis in Parkinson's dementia—new treatment provides hope

September 25, 2017
New research involving King's College London and the University of Exeter has highlighted the benefits of a promising new treatment which could relieve psychosis in thousands of people with dementia related to Parkinson's ...

Bicycling 'overloads' movement networks with Parkinson's

September 23, 2017
(HealthDay)—Bicycling suppresses abnormal beta synchrony in the Parkinsonian basal ganglia, according to a study published online Sept. 11 in the Annals of Neurology.

Researchers find new path to promising Parkinson's treatment

September 19, 2017
Three researchers at The University of Alabama are part of work that is leading to a new direction for drug discovery in the quest to treat Parkinson's disease.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.